ASPA rs28940880: Understanding Canavan Disease Carrier Status
The rs28940880 variant is a specific genetic change in the ASPA gene that results in a truncated, non-functional protein. It is primarily recognized as a marker for carrier status in individuals who may be at risk of passing on Canavan disease to their offspring.
What each genotype means
Typical ASPA genotype
This genotype represents the common, functional version of the ASPA gene. Individuals with this result do not carry the specific p.Tyr231Ter (c.693C>A) mutation associated with Canavan disease carrier status.
This is the most common genotype found in all populations worldwide.
Canavan disease carrier
This genotype indicates you are a carrier of the p.Tyr231Ter mutation in the ASPA gene. Carriers are typically asymptomatic and do not develop Canavan disease, which is an autosomal recessive condition, but you may pass this variant to your children.
This variant is most frequently observed in individuals of Ashkenazi Jewish descent, with a carrier frequency often cited between 1 in 40 and 1 in 55.
Potential Canavan disease risk
This genotype indicates the presence of two copies of the p.Tyr231Ter mutation. Because this mutation leads to a truncated, non-functional aspartoacylase enzyme, individuals with this result should consult with a medical geneticist or healthcare provider to discuss clinical implications and diagnostic testing.
This genotype is extremely rare in the general population.
What is the rs28940880 Variant?
The rs28940880 variant, also identified as c.693C>A or p.Tyr231Ter, is a nonsense mutation located within the ASPA gene. In genetics, a nonsense mutation is a change in the DNA sequence that introduces a premature stop signal. This signal tells the cell to stop building the protein before it is finished, resulting in a truncated, or shortened, version of the aspartoacylase enzyme. Because this protein is incomplete, it typically cannot perform its intended biological function. This variant is specifically cataloged as a marker for carrier status, meaning an individual carries one copy of the altered gene but does not necessarily exhibit the symptoms of the associated condition themselves.
The Role of the ASPA Gene
The ASPA gene provides the instructions for the body to produce an enzyme called aspartoacylase. This enzyme is essential for the proper function of the nervous system, particularly within the brain. Its primary job is to break down a compound known as N-acetyl-L-aspartic acid (NAA). NAA is found in high concentrations in neurons, and while its exact role is still being studied, it is believed that aspartoacylase helps maintain the health of the myelin sheath—the protective covering that insulates nerve fibers. When the ASPA gene is mutated and the enzyme is missing or non-functional, NAA accumulates in the brain, which is associated with the disruption of white matter and the development of Canavan disease.
Research and Clinical Significance
Research has firmly established that Canavan disease is an autosomal recessive disorder, meaning an individual must inherit two copies of a pathogenic mutation—one from each parent—to be affected. The rs28940880 variant is one of several known mutations in the ASPA gene that can lead to this condition. Because it is a nonsense mutation, its impact on protein function is significant. Clinical evidence supports its role as a pathogenic variant in the context of Canavan disease. However, it is important to note that the presence of this variant alone does not cause the disease in carriers. It is primarily used in clinical settings for carrier screening, particularly for couples who are planning a family and wish to understand the statistical risk of passing the condition to their children.
Population Frequency
The frequency of the rs28940880 variant varies significantly across different ancestral groups. It is most frequently observed in individuals of Ashkenazi Jewish descent, where carrier screening programs have been established due to the higher prevalence of this specific mutation compared to the general population. In the Ashkenazi Jewish population, the allele frequency is approximately 0.006, though estimates of carrier frequency for Canavan disease mutations in this group generally range from 1 in 40 to 1 in 82. In other ethnic populations, the incidence of this specific variant is much lower, and the overall prevalence of Canavan disease in those groups is considered rare and less well-documented.
Managing Genetic Information
Understanding your carrier status for a condition like Canavan disease is a personal decision that should be approached with professional guidance. If you have received results indicating you carry the rs28940880 variant, it is important to remember that this is not a medical diagnosis of a disease. You are encouraged to discuss these findings with a certified genetic counselor or a medical professional who can provide context based on your family history and reproductive goals. They can help explain the inheritance patterns, the likelihood of your partner also being a carrier, and the options available for family planning. This information is intended for educational purposes and should not be used to make independent medical decisions or to diagnose health conditions.
How common is this variant?
The rs28940880 variant is most notable in the Ashkenazi Jewish population, with an allele frequency of approximately 0.006, while it remains rare in other global populations.
Frequently asked questions
What is Canavan disease?
Canavan disease is a rare, inherited neurological disorder that causes the progressive degeneration of nerve cells in the brain. It is caused by mutations in the ASPA gene that prevent the breakdown of N-acetyl-L-aspartic acid.
Does being a carrier mean I have the disease?
No, being a carrier means you have one copy of the mutated gene but do not have the disease. Canavan disease is autosomal recessive, meaning it typically only affects individuals who inherit two copies of the mutation.
Should I get tested for this variant?
Carrier screening is often recommended for individuals of Ashkenazi Jewish descent or those with a family history of Canavan disease. You should discuss the benefits and implications of this testing with a genetic counselor.
Is there a cure for Canavan disease?
Currently, there is no cure for Canavan disease, and treatment is primarily supportive. However, research into gene therapies and other clinical interventions is ongoing.
Sources & further reading
Educational information only, last refreshed 9/23/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs28940880?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in ASPA
Pathogenic founder mutation (p.Tyr231Ter) associated with Canavan disease.
Pathogenic missense variant (p.Glu285Ala / E285A) causing aspartoacylase deficiency and carrier status for autosomal recessive Canavan disease.
Common pathogenic nonsense mutation (p.Tyr231Ter) in ASPA underlying Canavan disease.
Severe pathogenic ASPA nonsense mutation (p.Tyr231Ter) responsible for Canavan disease in reproductive carrier screening.
Pathogenic ASPA missense variant (p.Glu285Ala) causing aspartoacylase deficiency (Canavan disease), standardly tested in preconception carrier panels.
A missense mutation (c.854A>C, p.Glu285Ala) in aspartoacylase causing Canavan disease in the homozygous state, representing one of the most common Jewish carrier screening alleles.