ASPA rs77932196: Understanding the Glu285Ala Variant
The rs77932196 variant, also known as c.854A>C or p.Glu285Ala, is a specific genetic change in the ASPA gene. It is primarily recognized as a founder mutation associated with carrier status for Canavan disease, particularly within the Ashkenazi Jewish population.
What each genotype means
Typical aspartoacylase function
This genotype represents the common, non-pathogenic sequence for this position in the ASPA gene. Individuals with this profile do not carry the specific c.854A>C mutation associated with Canavan disease.
This is the most common genotype observed in all global populations.
Canavan disease carrier status
This genotype indicates you are a carrier of the c.854A>C (p.Glu285Ala) variant, which is a known pathogenic mutation for Canavan disease. As this condition is inherited in an autosomal recessive manner, carriers typically do not exhibit symptoms, but you should consult with a genetic counselor regarding reproductive risks.
This genotype is found in approximately 1 in 40 to 1 in 82 individuals of Ashkenazi Jewish ancestry, where it is a common founder variant.
Increased risk for Canavan disease
This genotype indicates the presence of two copies of the c.854A>C (p.Glu285Ala) variant, which is associated with Canavan disease, a rare autosomal recessive leukodystrophy. If you have this result, it is important to discuss these findings with a medical geneticist or healthcare provider for clinical evaluation and context.
This genotype is extremely rare in the general population and is primarily identified in individuals affected by Canavan disease.
What is the rs77932196 Variant?
The variant rs77932196 is a single nucleotide polymorphism (SNP) located within the ASPA gene on chromosome 17. In scientific literature, this specific change is often referred to as c.854A>C, which describes the substitution of an adenine base for a cytosine base at a specific position in the gene's DNA sequence. This change results in a missense mutation, meaning it alters the genetic code to produce a different amino acid in the resulting protein. Specifically, it replaces the amino acid glutamic acid with alanine at position 285 of the aspartoacylase enzyme. Because this variant is well-documented as a cause of Canavan disease when inherited in a homozygous state (two copies of the variant), it is a standard inclusion in many carrier screening panels designed to assess the risk of passing this condition to offspring.
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, specifically within cells known as oligodendrocytes, which are responsible for creating and maintaining the myelin sheath. Myelin is the protective, fatty covering that insulates nerve fibers and allows for the efficient transmission of electrical signals throughout the nervous system. Aspartoacylase functions by breaking down a substance called N-acetylaspartic acid (NAA) into aspartate and acetate. When the ASPA gene contains pathogenic mutations, the resulting enzyme may have significantly reduced or absent activity. This leads to an accumulation of NAA in the brain, which is believed to interfere with the normal development and maintenance of myelin, ultimately resulting in the spongy degeneration of white matter characteristic of Canavan disease.
Research and Clinical Significance
Research has firmly established that the p.Glu285Ala mutation is a major contributor to Canavan disease cases in the Ashkenazi Jewish population. Studies indicate that this variant, along with another common mutation (p.Tyr231Ter), accounts for the vast majority of disease-causing chromosomes in this group. The evidence for its pathogenicity is strong, as the mutant enzyme has been shown to retain only a small fraction of the activity of the wild-type enzyme. Because Canavan disease is an autosomal recessive condition, an individual must inherit two copies of a pathogenic variant—one from each parent—to be affected. Carriers, who possess only one copy of the variant, typically do not exhibit symptoms of the disease. The clinical focus for this variant is primarily on carrier screening to provide prospective parents with information regarding their reproductive risks.
Population Frequency
The frequency of the rs77932196 variant varies significantly across different ancestral groups. It is most frequently observed in individuals of Ashkenazi Jewish descent, where it is considered a founder mutation. In this population, the carrier frequency is often estimated to be between 1 in 40 and 1 in 82. Because of this relatively high prevalence, carrier screening for this specific variant is a standard practice in many clinical settings for individuals of Ashkenazi Jewish heritage. In contrast, the variant is much less common in the general global population, where other, different mutations in the ASPA gene may be more prevalent. Understanding these population-specific frequencies is essential for interpreting the results of genetic screening tests accurately and providing appropriate genetic counseling.
What This Information Means for You
If you have received information about your status regarding the rs77932196 variant, it is important to understand that this is a carrier status marker. Being a carrier means you have one copy of the variant and one functional copy of the gene, which generally does not cause health issues. However, if both parents are carriers of a pathogenic ASPA variant, there is a 25% chance with each pregnancy that the child will inherit two copies and be affected by Canavan disease. This information is intended for educational purposes and should not be used for self-diagnosis. If you are concerned about your carrier status or reproductive risks, the most appropriate step is to consult with a certified genetic counselor or a medical professional. They can help interpret your specific results in the context of your family history and provide guidance on appropriate testing or next steps.
How common is this variant?
The rs77932196 variant is a well-known founder mutation in the Ashkenazi Jewish population with a carrier frequency estimated between 1/40 and 1/82. It is significantly less common in the general global population.
Frequently asked questions
What is Canavan disease?
Canavan disease is a rare, inherited, and progressive neurodegenerative disorder that causes the breakdown of myelin in the brain. It is caused by mutations in the ASPA gene that lead to a deficiency of the enzyme aspartoacylase.
Does having the rs77932196 variant mean I have Canavan disease?
No, having one copy of the variant (being a carrier) does not mean you have the disease. Canavan disease is an autosomal recessive condition, meaning it typically only occurs when an individual inherits two pathogenic copies of the gene.
Should I get tested for this variant?
Carrier screening is often recommended for individuals of Ashkenazi Jewish descent who are planning a family. You should discuss the benefits and limitations of this testing with a healthcare provider or a genetic counselor.
Is there a cure for Canavan disease?
Currently, there is no cure for Canavan disease, and treatment is primarily supportive to manage symptoms. Research into gene therapies and other potential treatments is ongoing.
Sources & further reading
Educational information only, last refreshed 10/15/2026. 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.
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.