ASPA rs28940879: Understanding the p.Tyr231Ter Variant
The rs28940879 variant is a specific genetic change in the ASPA gene that results in a premature stop codon, known as p.Tyr231Ter. This variant is recognized as a pathogenic mutation associated with Canavan disease, a rare inherited condition that affects the central nervous system.
What each genotype means
Typical ASPA genotype
This genotype represents the common, functional version of the ASPA gene. Individuals with this profile do not carry the specific pathogenic mutation associated with Canavan disease at this location.
This is the most common genotype observed in the general population across all ancestries.
ASPA mutation carrier
This genotype indicates you carry one copy of the pathogenic variant (p.Tyr231Ter) in the ASPA gene. As Canavan disease is an autosomal recessive condition, carriers typically do not exhibit symptoms, but you may wish to discuss reproductive carrier screening options with a genetic counselor.
This genotype is found at an allele frequency of approximately 0.005 in the Ashkenazi Jewish population and is significantly rarer in other global populations.
Potential Canavan disease risk
This genotype indicates the presence of two copies of the pathogenic variant (p.Tyr231Ter) in the ASPA gene. This variant is associated with Canavan disease, a rare neurological disorder; if you have concerns regarding clinical symptoms or family history, please consult a medical geneticist or healthcare provider for diagnostic evaluation.
This genotype is extremely rare in the general population.
What is the rs28940879 Variant?
The rs28940879 variant, often referred to in clinical literature as p.Tyr231Ter or c.693C>A, is a nonsense mutation located within the ASPA gene. A nonsense mutation occurs when a change in the DNA sequence creates a premature stop signal, which instructs the cell to stop building a protein before it is complete. In this case, the mutation affects the production of the aspartoacylase enzyme. Because the protein is truncated, it typically cannot function correctly, leading to a loss of enzymatic activity. This specific variant is one of the well-documented genetic changes that can disrupt the normal biological processes managed by the ASPA gene, making it a significant focus in clinical genetics and reproductive carrier screening programs.
The Role of the ASPA Gene
The ASPA gene provides instructions for the body to produce an enzyme called aspartoacylase. This enzyme is primarily active in the brain, where it is responsible for breaking down a substance known as N-acetylaspartic acid (NAA). NAA is found in high concentrations in the brain, and its proper breakdown is essential for the maintenance of myelin, the protective sheath that covers nerve fibers. When the ASPA gene is mutated, as is the case with rs28940879, the resulting aspartoacylase deficiency leads to an accumulation of NAA in the brain. This buildup is associated with the disruption of myelin, a process that can lead to the spongy degeneration of white matter in the brain, which is the hallmark of Canavan disease.
Clinical Significance and Research
Research has firmly established rs28940879 as a pathogenic variant linked to Canavan disease, an autosomal recessive leukodystrophy. Because it is a recessive condition, an individual must typically inherit two copies of a pathogenic ASPA variant—one from each parent—to manifest the disease. The evidence for this variant's pathogenicity is strong, as it is one of the two primary founder mutations identified in the Ashkenazi Jewish population. Clinical studies have shown that this mutation, alongside others like p.Glu285Ala, accounts for the vast majority of Canavan disease cases within this specific ethnic group. While the evidence is robust for its role in disease development, it is important to note that clinical outcomes can vary, and genetic testing results should always be interpreted by a qualified medical geneticist or counselor.
Population Frequency
The frequency of the rs28940879 variant varies significantly across different ancestral populations. It is most frequently observed in individuals of Ashkenazi Jewish descent, where it is recognized as a founder mutation. In this population, the carrier frequency for Canavan disease-causing mutations is approximately 1 in 40. Outside of this group, the variant is much rarer. Population databases like gnomAD provide essential data on these frequencies, helping researchers understand the distribution of the variant globally. Because the variant is rare in the general population, it is not typically included in broad, non-targeted screening panels unless there is a specific clinical indication or family history that warrants testing for ASPA-related conditions.
Navigating Genetic Information
Understanding your carrier status for a variant like rs28940879 is a personal decision that should be made with the support of a healthcare professional. If you have received results indicating you are a carrier, it simply means you have one copy of the variant and are not expected to show symptoms of the condition yourself. However, it is important to discuss the implications of this result with a genetic counselor, especially if you are planning a family, as they can provide context on the risks of passing the variant to offspring. You cannot 'treat' or 'change' your genetic variant, but you can use this information to make informed reproductive health decisions. Always rely on clinical testing performed in certified laboratories rather than direct-to-consumer reports for medical decision-making.
How common is this variant?
The rs28940879 variant is most prevalent in the Ashkenazi Jewish population, with an allele frequency of approximately 0.005, while remaining very rare in other global populations.
Frequently asked questions
What is Canavan disease?
Canavan disease is a rare, inherited neurological disorder that causes the progressive breakdown of nerve cells in the brain. It is caused by a deficiency of the enzyme aspartoacylase, which leads to the accumulation of N-acetylaspartic acid.
Does being a carrier mean I have Canavan disease?
No, being a carrier means you have one copy of a pathogenic variant in the ASPA gene. Carriers typically do not show symptoms of the disease because they have a second, functional copy of the gene.
Should I get tested for rs28940879?
Genetic testing for this variant is typically recommended for individuals with a family history of Canavan disease or those from populations with a higher carrier frequency, such as the Ashkenazi Jewish community. You should discuss the necessity of this test with a genetic counselor or your primary care physician.
What happens if both parents are carriers?
If both parents are carriers of a recessive condition like Canavan disease, there is a 25% chance with each pregnancy that the child will inherit two copies of the variant and be affected by the disease. Genetic counseling is highly recommended in these situations to discuss reproductive options.
Sources & further reading
Educational information only, last refreshed 10/14/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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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.
Pathogenic ASPA missense variant (p.Glu285Ala) causing aspartoacylase deficiency (Canavan disease), standardly tested in preconception carrier panels.
A nonsense mutation (c.693C>A, p.Tyr231Ter) in ASPA leading to truncated aspartoacylase and defining carrier status for Canavan disease.
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.