ALMS1 in Sphynx Cats — What You Really Need to Know
Confused about ALMS1? You're not alone.
The ALMS1 test is a DNA test. It looks for a specific variant in a gene — it does NOT look at the heart. It was designed to indicate a possible future risk of HCM, not to diagnose existing disease.
Five years of research have answered many questions — but not the most important one.
The published evidence has NOT established that ALMS1 causes HCM.
The published evidence has NOT established that ALMS1 is irrelevant to HCM either.
Science does not simply classify ideas as "true" or "false". It weighs the strength of the available evidence. In a 2024 assessment, the ALMS1 variant was classified as a Variant of Uncertain Significance (VUS), meaning that there was not enough evidence to classify it confidently as either disease-causing or benign. In simple terms, there was not enough evidence to call it harmful, but there was not enough evidence to call it harmless either.
VUS is not a permanent label. It describes what the evidence shows at that point in time. With more research, a VUS can later be reclassified as pathogenic, likely pathogenic, likely benign or benign, so it can move in either direction.
As of 2026, the ALMS1 variant has NOT been formally reclassified in published research. It remains a VUS.
This article explains what each published study found, what it did not find, what the limitations were, and how our understanding of ALMS1 has changed over the past five years. The aim is not to tell you what decision to make. It is to help you understand the evidence, so you can make an informed one.
The ALMS1 variant has been studied in Sphynx cats since 2021. The original study reported a strong association with HCM, but later studies have not consistently reproduced that finding.
One phrase you will see repeatedly
When researchers say a finding is "statistically significant", they mean the result is unlikely to be a coincidence. When they say a result was NOT significant in the study group, they are not saying nothing is there. They are saying that, with the number of animals studied, they could not show that the difference was real rather than something that happened by chance.
Sometimes there really is no difference, but sometimes the study is simply too small to detect one. That matters here because several of the ALMS1 studies involve fairly small numbers of cats and short period of time.
Why was ALMS1 investigated?
ALMS1 attracted researchers' attention because it already had a recognised role in human medicine. Pathogenic variants in this gene cause Alström syndrome, a rare inherited disorder that can affect several organs, including the heart.
Studies in humans have shown that ALMS1 is involved in how heart muscle cells develop and maintain normal heart function. People with Alström syndrome may develop cardiomyopathy, most commonly dilated cardiomyopathy (DCM) in infancy or restrictive cardiomyopathy (RCM) later in life.
This made ALMS1 a reasonable gene to investigate in Sphynx cats with HCM. But having a good reason to investigate a gene is not the same as proving that it causes a disease. And that is where the story begins.
RESEARCH TIMELINE
2021 – Meurs et al. The study that started the ALMS1 story
In February 2021, Professor Kathryn Meurs and colleagues from North Carolina State University published the first study linking the ALMS1 c.7384G>C variant to hypertrophic cardiomyopathy (HCM) in Sphynx cats. This was the first study to report an association between the ALMS1 variant and HCM in the breed.
What did the researchers do?
The team studied 71 Sphynx cats diagnosed with HCM and compared them with 214 cats from 14 other breeds that had no known heart disease. They also examined heart tissue from affected cats to investigate how the variant might affect the heart.
What did they find?
The ALMS1 variant was found in 62 of the 71 affected Sphynx cats, compared with only 2 of 214 cats from other breeds. Based on these numbers, the researchers estimated that around three quarters of cats carrying the variant would be expected to develop the disease, and that carriers appeared many times more likely to be affected than non-carriers. These were estimates drawn from this particular group of cats, not from the breed as a whole. The reported estimate for penetrance was 77%.
However, one important finding is often overlooked: 9 cats with HCM did not carry the ALMS1 variant at all. The authors therefore concluded that ALMS1 was not the only genetic factor involved and that other causes of HCM were likely to exist in Sphynx cats. The affected cats also included cats carrying only one copy of the variant as well as cats carrying two copies.
Why wasn't this the final answer?
The researchers explained an important limitation of their study. The control group consisted of cats from other breeds, not healthy Sphynx cats. Because HCM can develop later in life, it is difficult to identify young Sphynx cats that can confidently be considered unaffected for life.
For this reason, the study found a strong association, but it could not tell us whether the variant itself was causing the disease or whether it was simply very common in Sphynx cats.
Why does this study still matter today?
This study changed the direction of feline cardiology research. It identified ALMS1 as a promising gene to investigate and led to further studies in different cat populations.
2023 – Akiyama et al. Looking beyond the Sphynx breed
After the 2021 study, one important question remained unanswered: Was the ALMS1 variant unique to Sphynx cats, or could it also be found in other breeds? Researchers in Japan looked for the same variant in cats from several breeds.
What did the researchers do?
They looked for ALMS1 in breeds including Scottish Fold, Munchkin, American Shorthair, Exotic Shorthair and Minuet. They also compared 18 Scottish Fold cats with HCM with 132 Scottish Fold cats from the general population.
What did they find?
The ALMS1 variant was not unique to Sphynx cats. It was found in several other breeds where it had not previously been reported. The study did not find a statistically significant difference between the Scottish Fold cats with HCM and the general Scottish Fold population.
Why was this important?
This changed how the original 2021 findings could be interpreted. The fact that the variant was rare in the original control group may have reflected which breeds were selected as controls, rather than showing that ALMS1 was rare outside the Sphynx breed.
Did this prove ALMS1 was harmless?
No. The study did not show that ALMS1 was harmless or irrelevant. It showed that the variant existed in more breeds than previously thought and that this particular study did not find a significant association with HCM in Scottish Fold cats.
2023 – Turba et al. Why the test itself also needed checking
While researchers were still trying to understand what ALMS1 might mean, an Italian team found a different problem: Could the DNA test sometimes give the wrong result?
What did the researchers do?
The team tested 136 Sphynx cats for the ALMS1 variant. In one family, the result did not match what should have been inherited from parent to kitten. That suggested the test had failed to detect one copy correctly.
What did they find?
The researchers discovered five previously unknown DNA changes close to the ALMS1 variant. Three were located exactly where the original test attached to the DNA. Because of this, one copy could sometimes be missed. This is known as allele drop-out. The team redesigned the test to avoid the problem.
Why was this important?
This study is sometimes taken to mean that ALMS1 testing as a whole was proven unreliable. That is not what it showed. It found a problem with the original test design and showed how the test could be redesigned to avoid allele drop-out.
It also showed just how common ALMS1 was in this population. The researchers gave a detailed breakdown for the 59 cats aged four years or under: 14 of them carried two copies of the variant, 27 carried one copy, and only 18 carried none. That is 41 of the 59 younger cats carrying at least one copy.
The authors said that more heart examinations and follow-up were still needed to understand how the DNA results related to actual HCM diagnoses.
2024 – Boeykens et al. The study that formally classified ALMS1
By 2024, several feline DNA variants were being sold or discussed as tests for HCM. Researchers therefore asked a basic question: How strong is the evidence behind each one?
What did the researchers do?
An international team of feline genetics and cardiology experts reviewed six published variants previously linked with HCM in different cat breeds. They used an established system for judging genetic evidence and adapted it for veterinary genetics.
The system considers things such as how common a variant is, whether it appears more often in affected animals, whether it follows disease through families and whether laboratory studies support a harmful effect.
What did they find?
For ALMS1, there was not enough evidence to call the variant clearly disease-causing or clearly benign. It was classified as a Variant of Uncertain Significance, or VUS.
There is an important part of this assessment that is easy to miss. ALMS1 is very common in Sphynx cats. Usually, when a variant is extremely common in a population, that can count as evidence against it causing a serious disease. But cat breeds are not the same as large human populations. A genetic change can become very common within a breed simply because the breeding population is much smaller and more closely related.
The high frequency of ALMS1 therefore counted as evidence towards benign, but it was not enough to classify it as likely benign or benign. It remained a VUS.
The study also included its own Sphynx case-control data. 53 Sphynx cats with HCM were compared with 31 Sphynx cats aged six years or older that had normal echocardiograms. ALMS1 was not associated with HCM in this comparison (allelic odds ratio 1.02) — the variant was essentially no more common in affected cats than in these older, apparently unaffected controls.
The age of the control cats matters. HCM is an age-dependent disease, so using cats aged six years or older with normal heart scans provides a more informative comparison than using young cats that may simply not have developed detectable disease yet. However, even a normal echocardiogram at six years of age cannot prove that a cat will remain free of HCM for life.
The authors also stated that a variant of unknown significance should not influence clinical decision-making.
Did VUS mean "irrelevant"?
No. VUS means uncertain, not irrelevant. It tells us that the available evidence cannot yet answer the question reliably in either direction. A VUS can later move towards disease-causing or towards benign as more evidence becomes available.
Before we go further, there are two things which matter when interpreting these studies: PENETRANCE and AGE
Penetrance
Penetrance sounds complicated, but the basic idea is simple. If a genetic variant has incomplete penetrance, not every animal carrying it will develop the disease.
The original researchers estimated penetrance at 77%. Under that model, some cats could carry ALMS1 and never develop HCM. It would also be possible for a parent carrying the variant to have normal heart scans while an offspring carrying the same variant developed HCM.
We need to be careful with that 77% figure now, because later studies have questioned the strong ALMS1 and HCM link behind the original estimate. It should not be treated as the known lifetime risk for an ALMS1-positive Sphynx cat. But the idea of incomplete penetrance still matters.
Age
Finding healthy cats that carry a variant does not, by itself, prove that the variant is harmless. A young cat with a normal echocardiogram cannot automatically be considered unaffected for life. HCM may become apparent later.
To understand what happens to carriers and non-carriers properly, researchers need to follow cats as they get older. And that brings us to New Zealand.
2024 – Seo et al. Following the same cats over time
The New Zealand study added something particularly useful: follow-up. Rather than looking at the cats only once, the researchers invited the same Sphynx cats back for another heart examination to see what happened over time.
What did the researchers do?
The team examined 55 apparently healthy Sphynx cats using echocardiography, or heart ultrasound. The cats were also tested for ALMS1. 11 cats had two copies of the variant, 28 had one copy, and 16 did not carry it.
What did they find at the first examination?
12 cats had HCM. 1 of the 11 cats with two copies of ALMS1 had HCM. 7 of the 28 cats with one copy had HCM, and 4 of the 16 cats without the variant had HCM.
The fact that most cats with two copies did not have HCM at that examination does not by itself prove that the variant is harmless. The original hypothesis did not assume that every cat carrying the variant would develop HCM, and HCM can also become apparent later in life. A normal scan at one point in time therefore cannot tell us what will happen to those cats as they get older.
What happened at follow-up?
42 cats returned for another cardiac examination after a median of 1.8 years ( 22 months). Another 11 cats were found to have HCM. 10 of those 11 carried ALMS1: 2 had two copies, 8 had one copy, and only 1 did not carry the variant.
There is one important detail in the final numbers. One cat diagnosed with HCM at the first examination later had normal heart measurements. Because there was no further follow-up to establish whether the original thickening had been temporary, the researchers removed that cat from the final HCM group.
In the main results, the authors describe 22 cats as having HCM during the study. Of those 22 cats, 17 carried ALMS1 and five did not. That means 77.3% of the cats described as having HCM in the main results carried ALMS1.
But there is an important piece of context: ALMS1 was already extremely common in the whole study group. Around 71% of all 55 cats carried it, including many cats without HCM. So finding ALMS1 in most of the cats with HCM did not automatically mean that the variant was responsible for their disease.
The researchers did not find a statistically significant association between ALMS1 and HCM in this group. This is important evidence against ALMS1 being a strong, simple predictor of HCM. But it cannot tell us that the variant has no effect at all, or whether an effect might be smaller or only become clear as cats get older.
There is a small numerical inconsistency in the published paper that is worth mentioning. The abstract says that 20 of the 55 cats had HCM and calls this 40%. But 20 out of 55 is about 36%, not 40%. The main results describe 22 cats with HCM, and 22 out of 55 is 40%. The genotype results are also given for those 22 cats.
What did the family tree show?
The researchers also looked at how HCM appeared within a large family of related Sphynx cats. The pattern suggested that HCM itself can be inherited even when a parent does not develop the disease. Importantly, this finding was about HCM in Sphynx cats, not about ALMS1 specifically.
Why was this study important?
This was the first study to follow the same Sphynx cats over time. By the end of the study, HCM had been found in approximately 40% of the cats, including cats whose first heart examination had been normal.
That 40% should not be treated as the lifetime risk either. The cats were not followed for their entire lives, and some cats without HCM could still develop it later. The study therefore demonstrated something particularly important for breeders and owners: a normal heart scan today does not guarantee a normal heart for life.
Was that the end of the story?
No. One cat that had a normal heart scan at the beginning later developed dilated cardiomyopathy (DCM). That cat carried one copy of ALMS1.
The researchers did not conclude that ALMS1 caused DCM. They pointed out that dilated and restrictive cardiomyopathy occur in human Alström syndrome and said that more cases would be needed before anyone could know whether there might be a connection in Sphynx cats.
The authors also suggested that the high frequency of ALMS1 in Sphynx cats may help explain why the original 2021 study found such a large difference between affected Sphynx cats and cats from other breeds.
2026 – Dargar, Abitbol et al. Looking beyond cats: what happens inside heart cells?
By 2026, researchers asked a different question. Instead of asking whether ALMS1 appeared more often in cats with HCM, they asked: Does this genetic change have any measurable biological effect at all?
What did the researchers do?
This was not a study of cats. The researchers used human laboratory cells that can be turned into heart muscle cells. They introduced the human equivalent of the feline ALMS1 variant and compared those cells with otherwise similar cells without the change.
What did they find?
Cells carrying two copies of the variant produced significantly fewer heart muscle cells. But the heart muscle cells that did develop did not show significant differences in several of the main things the researchers measured. They contracted at a similar rate, were a similar size and had similarly organised internal structures.
So the clearest effect was on how efficiently the cells developed into heart muscle cells, rather than an obvious problem in the heart muscle cells that successfully formed.
Does this prove ALMS1 causes HCM in Sphynx cats?
No. These were human cells in a laboratory, not living Sphynx cats. The study showed that the variant had a measurable biological effect in this model. It did not show that the same effect causes HCM in cats.
Could ALMS1 be doing something more subtle?
Possibly. The researchers suggested another possibility: ALMS1 might influence disease without being its main cause. In other words, the variant might affect whether, when or how strongly disease develops when other genetic or biological factors are also involved.
That idea has not been demonstrated in living Sphynx cats. It is another possibility that now needs to be investigated.
What did the authors conclude?
The authors said more research was needed. Importantly, they also supported the previous recommendation not to use this ALMS1 variant to select breeding cats until there is stronger evidence that the variant itself causes disease.
That does not mean ALMS1 has been shown to be irrelevant. It means we still do not know enough to treat it as a proven disease-causing mutation.
2026 – Sussadee et al. One more population, the same question
Researchers in Thailand returned to the original question: Is ALMS1 associated with HCM in Sphynx cats?
What did the researchers do?
The team examined 47 Sphynx cats. The median age was only 24 months. Each cat had a DNA test and a heart ultrasound.
Unlike the New Zealand study, the cats were examined only once, so we do not know what happened to their hearts as they got older.
The ALMS1 variant was found in 21 of the 47 cats, or 44.68%. 18 cats had one copy, 3 had two copies, and 26 did not carry it.
What did they find?
Only 4 cats in the entire study had HCM. Two carried one copy of ALMS1. The other two did not carry the variant.
None of the three cats carrying two copies had HCM, but those three cats were particularly young, with a median age of only 10 months.
The researchers found no statistically significant association between ALMS1 and HCM in this group. They also found no significant link between the DNA result and the detailed heart measurements taken during the scans.
What did the authors conclude?
The authors concluded that, in their study population, ALMS1 was unlikely to be the primary cause of HCM. They did not conclude that the variant was harmless or irrelevant.
Why was this study important?
It provided another independent Sphynx population in which the original strong association from 2021 was not reproduced. Its findings were also consistent with the uncertainty reflected in the 2024 assessment, where ALMS1 had been classified as a Variant of Uncertain Significance.
Where does the evidence leave us today?
After five years of research, several things have become clearer. The strong association reported in 2021 has not been consistently reproduced in independent Sphynx populations. At the same time, the evidence has not established that ALMS1 is biologically irrelevant. Instead, each study has added another piece to the picture.
One thing is particularly clear: ALMS1 is common in Sphynx cats. In the Italian study, 41 of the 59 younger cats for whom the researchers provided this genotype breakdown carried at least one copy. In New Zealand, 39 of 55 cats carried it, and in Thailand, 21 of 47 did. Although these groups are not directly comparable, all three studies found ALMS1 frequently in the Sphynx cats they examined.
Today we know that:
ALMS1 cannot explain all HCM in Sphynx cats. Cats without the variant also develop the disease.
ALMS1 remains a Variant of Uncertain Significance, or VUS.
A biological effect has been found in laboratory cells, but we do not know what that means for living Sphynx cats.
Researchers have raised the possibility that ALMS1 could influence disease without being its main cause, but this hypothesis has not been demonstrated in cats.
The evidence does not currently support treating ALMS1 as a proven cause of HCM.
The DNA test cannot replace heart screening.
We also need to remember that "no statistically significant association was found in this study group" and "there is no association" are not the same statement.
Sometimes science gives us an inconvenient answer. For ALMS1, that answer is still:
We do not know yet.
Describing ALMS1 as either "a proven cause of HCM" or "irrelevant" goes beyond what the published evidence currently supports.
What does this mean for buyers?
If you are buying a Sphynx kitten, the first priority should be the health of the breeding cats. Ask whether the parents are regularly examined by a veterinary cardiologist, how often they are rescanned and whether you can see their most recent echocardiography reports.
A DNA test should never replace cardiac screening. But ALMS1 should not simply be ignored either. It is currently a Variant of Uncertain Significance. That means we do not yet know whether it increases the risk of disease, has no meaningful effect, or perhaps influences the heart only together with other factors.
That classification may change as more evidence becomes available. Nobody currently knows in which direction. Some buyers may therefore prefer to avoid the variant. Others may decide that the evidence is not strong enough for ALMS1 to influence their choice.
Both approaches are reasonable, provided the decision is based on a correct understanding of what a Variant of Uncertain Significance actually means.
What does this mean for breeders?
The current evidence does not support using ALMS1 as a stand-alone breeding test. At the same time, it does not support ignoring the variant or describing it as biologically irrelevant.
The best available tool for detecting HCM in breeding cats remains regular echocardiographic screening by an experienced veterinary cardiologist.
HCM is an age-dependent disease. A cat with a normal heart scan at one or two years old may still develop HCM later. The New Zealand study showed this clearly: some cats had normal scans at the beginning and were later diagnosed with HCM. For that reason, repeated heart screening as breeding cats get older is much more informative than relying on a single scan before the first litter.
But even years of normal scans in both parents cannot make a breeding line risk-free. HCM can still occur in their offspring.
So what should a breeder do with an ALMS1 result?
The current evidence does not justify automatically removing every carrier from breeding. There are two important reasons.
First, ALMS1 is still a Variant of Uncertain Significance. We do not have enough evidence to say that carrying it causes HCM. Second, the variant is common in the breed. Removing large numbers of otherwise valuable cats because of a VUS could unnecessarily reduce genetic diversity and create other problems.
But avoiding blanket exclusion does not mean the result has to be ignored. There is a difference between removing every carrier from breeding and managing an uncertain variant gradually.
A breeder may decide to keep a valuable carrier because of its wider genetics, family history, health and cardiac screening. If that cat later produces several equally suitable offspring, the breeder may choose an ALMS1-clear offspring to continue the line. That is one possible way of gradually moving away from the variant without treating the original carrier as though it has a proven disease-causing mutation.
Another breeder may reasonably decide not to select for ALMS1 at all until its significance becomes clearer. Current research does not tell us that either approach is scientifically settled.
We do not know that breeding away from ALMS1 will reduce HCM. We also do not know that ALMS1 is harmless. For now, breeding decisions should still be driven mainly by repeated heart screening, age, family history, overall health and genetic diversity.
ALMS1 can remain part of that information, but it should not outweigh everything else while we still do not know what it means.
References:
Meurs KM, Williams BG, DeProspero D, Friedenberg SG, Malarkey DE, Ezzell JA, Keene BW, Adin DB, DeFrancesco TC, Tou S. A deleterious mutation in the ALMS1 gene in a naturally occurring model of hypertrophic cardiomyopathy in the Sphynx cat. Orphanet Journal of Rare Diseases. 2021;16:108. doi:10.1186/s13023-021-01740-5. PMID: 33639992
Akiyama N, Suzuki R, Saito T, Yuchi Y, Ukawa H, Matsumoto Y. Presence of known feline ALMS1 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy in Japan. PLoS ONE. 2023;18(4):e0283433. doi:10.1371/journal.pone.0283433. PMID: 37071642
Turba ME, Ferrari P, Milanesi R, Gentilini F, Longeri M. HCM-associated ALMS1 variant: allele drop-out and frequency in Italian Sphynx cats. Animal Genetics. 2023;54:643–646. doi:10.1111/age.13340. PMID: 37345275
Boeykens F, Abitbol M, Anderson H, Dargar T, Ferrari P, Fox PR, Hayward JJ, Häggström J, Davison S, Kittleson MD, van Steenbeek F, Ljungvall I, Lyons LA, Longeri M, Ohlsson Å, Peelman L, Dufaure de Citres J, Smets P, Turba ME, Broeckx BJG. Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines. Frontiers in Veterinary Science. 2024;11:1327081. PMID: 38371598. (Correction: Frontiers in Veterinary Science. 2024;11:1458433.)
Seo J, Loh Y, Connolly DJ, Luis Fuentes V, Dutton E, Hunt H, Munday JS. Prevalence of hypertrophic cardiomyopathy and ALMS1 variant in Sphynx cats in New Zealand. Animals. 2024;14(18):2629. doi:10.3390/ani14182629. PMID: 39335220
Dargar T, Janin A, Risson V, Lafont E, Valla C, Gache V, Abitbol M. Characterisation of a missense variant of the Alström syndrome centrosome and basal body associated protein (ALMS1) gene associated with cardiomyopathy using induced pluripotent stem cells. Genes. 2026;17(2):227. doi:10.3390/genes17020227
Sussadee M, Jarudecha T, Muikaew R, Supaphom K, Rucksaken R, Sukumolanan P. Prevalence and clinical relevance of Alström syndrome protein 1 gene variant and feline hypertrophic cardiomyopathy in Sphynx cats in Thailand. Animals. 2026;16(12):1815. doi:10.3390/ani16121815
Background: ALMS1 and Alström syndrome in humans
Marshall JD, Beck S, Maffei P, Naggert JK. Alström syndrome. European Journal of Human Genetics. 2007;15:1193–1202. doi:10.1038/sj.ejhg.5201933
Shenje LT, Andersen P, Halushka MK, et al. Mutations in Alström protein impair terminal differentiation of cardiomyocytes. Nature Communications. 2014;5:3416. doi:10.1038/ncomms4416
Louw JJ, Corveleyn A, Jia Y, et al. Homozygous loss-of-function mutation in ALMS1 causes the lethal disorder mitogenic cardiomyopathy in two siblings. European Journal of Medical Genetics. 2014;57:532–535. doi:10.1016/j.ejmg.2014.06.004
Database record
OMIA:002316-9685 — Cardiomyopathy, hypertrophic, ALMS1-related in Felis catus. Online Mendelian Inheritance in Animals. https://www.omia.org