ASPA rs28940878: Understanding Canavan Disease Carrier Status
The rs28940878 variant is a specific genetic change in the ASPA gene associated with Canavan disease, a rare neurological condition. It is primarily studied in the context of carrier screening, particularly for individuals of Ashkenazi Jewish descent.
What each genotype means
Typical ASPA genotype
This genotype represents the common, non-pathogenic sequence at this position in the ASPA gene. It is not associated with the development of Canavan disease.
This is the most common genotype found in the general population across all ancestries.
ASPA variant carrier
You carry one copy of the p.Glu285Ala pathogenic variant, which is associated with Canavan disease when two copies are present. As an autosomal recessive condition, carriers typically do not exhibit symptoms of the disease, but you should discuss reproductive risks and carrier testing with a genetic counselor or clinician.
This genotype is found in approximately 1 in 33 individuals of Ashkenazi Jewish ancestry, with significantly lower frequencies in other populations.
Increased risk for Canavan disease
This genotype indicates the presence of two copies of the p.Glu285Ala pathogenic variant, which is known to cause a complete loss of aspartoacylase activity. This state is clinically associated with typical Canavan disease, a neurodegenerative disorder; please consult with a medical geneticist or specialist for clinical evaluation and management.
This genotype is extremely rare in the general population, occurring primarily in individuals of Ashkenazi Jewish descent.
What is the rs28940878 Variant?
The rs28940878 variant is a single nucleotide polymorphism (SNP) located within the ASPA gene on chromosome 17. In genetic terms, this variant represents a missense mutation, specifically identified as p.Glu285Ala. This means that at a specific position in the genetic code, a single DNA building block is altered, which results in the substitution of one amino acid for another in the resulting protein. Because the ASPA gene provides the instructions for creating the aspartoacylase enzyme, changes like rs28940878 can potentially disrupt the enzyme's normal function. This variant is well-documented in clinical databases as a pathogenic mutation, meaning it is known to contribute to the development of disease when inherited in a specific pattern.
The Role of the ASPA Gene
The ASPA gene is responsible for producing an enzyme called aspartoacylase. This enzyme plays a critical role in the brain by breaking down a compound known as N-acetylaspartic acid (NAA). NAA is essential for the maintenance of white matter, the tissue that allows different parts of the brain to communicate effectively. When the ASPA gene contains pathogenic variants, the body may produce insufficient or non-functional aspartoacylase. This leads to an accumulation of NAA in the brain, which is toxic to the white matter. This process, known as spongy degeneration or leukodystrophy, is the underlying cause of Canavan disease. The severity of the condition often correlates with how much enzyme activity is lost due to the specific genetic variants present.
Clinical Significance and Evidence
The association between the ASPA gene and Canavan disease is considered definitive by clinical genetics organizations. The rs28940878 variant is specifically recognized as a pathogenic mutation that causes aspartoacylase deficiency. Because Canavan disease is an autosomal recessive condition, an individual must typically inherit two copies of a pathogenic variant—one from each parent—to manifest the disease. If a person carries only one copy, they are considered a carrier and generally do not show symptoms of the condition. Due to its clear link to the disease, this variant is a standard component of preconception and prenatal carrier screening panels. While the evidence for its pathogenicity is strong, clinical outcomes can vary, and genetic counseling is recommended to interpret individual test results accurately.
Population Frequency
The frequency of the rs28940878 variant is not uniform across all human populations. It is notably more common in individuals of Ashkenazi Jewish descent due to a historical founder effect, where a specific genetic trait becomes more prevalent in a population that descends from a small number of ancestors. Research indicates that the carrier frequency for Canavan disease-related variants in the Ashkenazi Jewish population is significantly higher than in the general population, with estimates often cited between 1 in 40 and 1 in 82. In contrast, the variant is much rarer in other ethnic groups. Understanding these population-specific frequencies is a cornerstone of modern genetic screening, helping clinicians provide more relevant risk assessments for prospective parents.
What You Can Do With This Information
If you receive information about your status regarding the rs28940878 variant, it is important to view it as a piece of information for family planning rather than a medical diagnosis. If you are identified as a carrier, it simply means you have one copy of the variant, which does not cause Canavan disease in you. However, if your partner is also a carrier of a pathogenic ASPA variant, there may be a risk of passing the condition to future children. This information is best discussed with a certified genetic counselor or a medical professional who can explain the inheritance patterns and the implications for your family. Never make reproductive or medical decisions based solely on raw genetic data; always seek professional guidance to understand the context and accuracy of your results.
How common is this variant?
The rs28940878 variant is significantly enriched in the Ashkenazi Jewish population, with an allele frequency of approximately 0.015, compared to much lower frequencies 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 white matter in the brain. It is caused by mutations in the ASPA gene that lead to a deficiency of the enzyme aspartoacylase.
Does being a carrier for rs28940878 mean I have the disease?
No, being a carrier means you have one copy of the variant, but you do not have the disease. Canavan disease is an autosomal recessive condition, meaning it typically requires two copies of a pathogenic variant to manifest.
Why is this variant tested in Ashkenazi Jewish populations?
This variant is more common in the Ashkenazi Jewish population due to a founder effect. Because of this higher prevalence, it is standard practice to include it in carrier screening panels for this demographic.
Is there a cure for Canavan disease?
Currently, there is no cure for Canavan disease. Treatment is focused on managing symptoms and providing supportive care, though research into gene therapy and other experimental treatments is ongoing.
Sources & further reading
Educational information only, last refreshed 9/27/2026. 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.
Severe pathogenic ASPA nonsense mutation (p.Tyr231Ter) responsible for Canavan disease in reproductive carrier screening.
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.
A nonsense mutation (c.693C>A, p.Tyr231Ter) in ASPA leading to truncated aspartoacylase and defining carrier status for Canavan disease.