ASPA rs76151636: Understanding the Y231X Variant
The rs76151636 variant in the ASPA gene is a well-documented nonsense mutation, also known as p.Tyr231Ter or Y231X. It is primarily recognized as a pathogenic variant associated with carrier status for Canavan disease, particularly within 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. Individuals with this genotype do not carry the specific p.Tyr231Ter mutation associated with Canavan disease at this locus.
This is the most common genotype observed across all global populations.
Canavan disease carrier
This genotype indicates you are a carrier of the p.Tyr231Ter (also known as p.Y231X) mutation in the ASPA gene. Canavan disease is an autosomal recessive condition, meaning carriers typically do not show symptoms, but should discuss reproductive risks and genetic counseling with a healthcare provider.
This genotype is found in approximately 1 in 40 to 1 in 60 individuals of Ashkenazi Jewish descent, and is significantly rarer in other populations.
Potential Canavan disease risk
This genotype indicates the presence of two copies of the p.Tyr231Ter (p.Y231X) mutation. This mutation is a well-established cause of Canavan disease, an inherited leukodystrophy characterized by aspartoacylase deficiency and neurological impairment. Individuals with this result should consult with a medical geneticist or specialist for clinical evaluation.
This genotype is extremely rare, occurring only in individuals affected by Canavan disease.
What is the rs76151636 Variant?
The rs76151636 variant is a specific change in the DNA sequence of the ASPA gene, located on chromosome 17. In scientific literature, this variant is frequently referred to as p.Tyr231Ter or Y231X, indicating that it introduces a premature stop codon in the protein-coding sequence. This type of mutation, known as a nonsense mutation, typically results in the production of a truncated, non-functional protein. Because the ASPA gene provides the blueprint for the enzyme aspartoacylase, this alteration prevents the body from producing a fully functional version of this essential protein. This variant is one of the primary genetic markers screened for in populations where it is known to be prevalent, as it is a significant contributor to the genetic architecture of Canavan disease.
The Role of the ASPA Gene
The ASPA gene is responsible for producing the enzyme aspartoacylase, which is critical for the health of the central nervous system. This enzyme is primarily found in specialized brain cells called oligodendrocytes, which are responsible for maintaining myelin—the protective sheath that insulates nerve fibers. Aspartoacylase functions by breaking down a substance called N-acetylaspartate (NAA) into aspartate and acetate. When the ASPA gene is mutated and the enzyme is deficient, NAA accumulates in the brain. This buildup is toxic to the myelin sheath, leading to a condition known as spongy degeneration or leukodystrophy. This process disrupts the normal communication between nerve cells, which is why mutations in this gene are linked to the progressive neurological symptoms observed in Canavan disease.
Research and Clinical Significance
Research has firmly established rs76151636 as a pathogenic variant. It is one of two major 'founder mutations'—along with p.Glu285Ala—that account for the vast majority of Canavan disease cases in the Ashkenazi Jewish population. The evidence for its pathogenicity is strong, as it directly leads to a loss of enzyme function. However, it is important to note that being a carrier of this variant does not mean an individual will develop the disease. Canavan disease is an autosomal recessive condition, meaning an individual must inherit two non-working copies of the gene (one from each parent) to manifest symptoms. Carriers, who possess one functional copy and one copy with the rs76151636 variant, typically remain healthy and asymptomatic. Clinical guidelines often recommend carrier screening for individuals of Ashkenazi Jewish descent to provide information for family planning.
Population Frequency and Ancestry
The frequency of the rs76151636 variant is notably higher in the Ashkenazi Jewish population compared to the general global population. This is attributed to the 'founder effect,' where a small, historically isolated group expanded, causing specific genetic variants to become more concentrated over generations. Estimates for the carrier frequency of Canavan disease-causing mutations in this population generally range from 1 in 40 to 1 in 60. Because of this elevated risk, many medical organizations and genetic counseling services include this variant in standard reproductive carrier screening panels for those of Ashkenazi Jewish ancestry. While the variant is most common in this specific group, it can occur in other populations, though at significantly lower frequencies. Understanding these population-specific patterns is a cornerstone of modern clinical genetics and reproductive health.
Navigating Genetic Information
If you have received information regarding your status for the rs76151636 variant, it is important to understand what this means in a practical context. A 'carrier' result indicates that you have one copy of the variant, which does not cause health issues for you personally. However, if both partners are carriers of a pathogenic ASPA variant, there is a 25% chance with each pregnancy that a child could inherit two copies and develop Canavan disease. This information is intended for educational purposes and should not be used to make medical decisions without professional guidance. If you are concerned about your carrier status or family planning, you should consult with a certified genetic counselor or your primary healthcare provider. They can help interpret your results, discuss the implications for your family, and provide context based on your specific medical history.
How common is this variant?
The rs76151636 variant is significantly enriched in the Ashkenazi Jewish population, with carrier frequencies estimated between 1 in 40 and 1 in 60.
Frequently asked questions
What is a carrier of Canavan disease?
A carrier is an individual who has one copy of a mutated ASPA gene and one normal copy. Carriers do not have the disease and are typically healthy.
Should I get tested for the rs76151636 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 genetic counselor or your doctor.
Can I develop Canavan disease if I am a carrier?
No, carriers of the rs76151636 variant do not develop Canavan disease. The condition is autosomal recessive, requiring two mutated copies of the gene to manifest.
Is there a treatment for Canavan disease?
Currently, there is no cure for Canavan disease, and management focuses on supportive care. Research into gene therapies and other interventions is ongoing.
Sources & further reading
Educational information only, last refreshed 10/13/2026. 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.
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.
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.