ASPA rs121907987: Understanding the E285A Variant
The rs121907987 variant, also known as p.Glu285Ala or E285A, is a specific change in the ASPA gene. It is recognized as a pathogenic variant associated with carrier status for Canavan disease, an autosomal recessive neurodegenerative disorder.
What each genotype means
Typical enzyme activity
You carry two copies of the reference allele and do not harbor the E285A pathogenic variant in the ASPA gene. Research indicates typical aspartoacylase enzyme function and standard baseline population risk for Canavan disease. However, standard testing for this single site does not rule out being a carrier for other rare variants elsewhere in ASPA.
Carried by more than 98% of individuals of Ashkenazi Jewish ancestry and over 99.9% of individuals across most other global populations.
Canavan disease carrier
You carry one copy of the pathogenic E285A missense variant, identifying you as an asymptomatic carrier for autosomal recessive Canavan disease. Because Canavan disease requires two nonfunctional ASPA alleles to develop, single-copy carriers typically experience no health symptoms. If planning a family, genetic counseling and partner screening are commonly discussed to evaluate reproductive risk.
Carried by approximately 1 in 40 to 1 in 80 individuals (around 1.2% to 2.5%) of Ashkenazi Jewish ancestry, but observed in fewer than 1 in 1,000 individuals in broader global populations.
Canavan disease risk
You carry two copies of the pathogenic E285A variant, which published literature associates with a loss of aspartoacylase catalytic activity and typical severe Canavan disease. Because Canavan disease is a severe infantile neurodegenerative condition that typically presents in early infancy, adults with this genotype should discuss testing verification and clinical correlation with a medical geneticist.
Extremely rare globally, estimated at less than 1 in 10,000 even in founder populations of Ashkenazi Jewish ancestry.
What is the rs121907987 Variant?
The rs121907987 variant is a single nucleotide polymorphism (SNP) located within the ASPA gene on chromosome 17. In genetic notation, this variant is frequently referred to as p.Glu285Ala or E285A, indicating that the amino acid glutamic acid is replaced by alanine at position 285 of the resulting protein. This specific change is classified as a pathogenic missense variant. Because Canavan disease is inherited in an autosomal recessive pattern, an individual must typically inherit two copies of a pathogenic variant—one from each parent—to manifest the condition. Carriers, who possess only one copy of this variant, generally do not show symptoms of the disease but can pass the variant to their children. Understanding this variant is a key component of carrier screening programs, particularly for those with specific ancestral backgrounds where this mutation is more prevalent.
The Role of the ASPA Gene
The ASPA gene provides instructions for producing an enzyme called aspartoacylase. This enzyme is primarily active in the brain, where it plays a critical role in 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 and facilitates efficient signal transmission. When the ASPA gene contains pathogenic mutations like rs121907987, the resulting aspartoacylase enzyme may have significantly reduced or absent activity. This leads to an accumulation of NAA in the brain, which is thought to interfere with the growth and maintenance of myelin. The resulting disruption in nerve signaling is the underlying cause of the neurological symptoms observed in Canavan disease, which can include developmental delays, loss of motor skills, and other severe neurological complications.
Research and Clinical Significance
The rs121907987 variant is one of the most well-documented mutations associated with Canavan disease. Extensive research has established that this variant, along with others like p.Tyr231Ter, accounts for the vast majority of pathogenic ASPA alleles in individuals of Ashkenazi Jewish descent. Studies have shown that the E285A mutant enzyme retains only a small fraction—approximately 2.5% to 3%—of the activity found in the normal, wild-type enzyme. Because of this severe loss of function, the variant is classified as pathogenic in clinical databases like ClinVar. While the evidence linking this variant to Canavan disease is strong, it is important to note that clinical diagnosis is complex. The presence of this variant in a carrier state does not cause the disease, and genetic testing results should always be interpreted by a qualified genetic counselor or medical professional who can provide context based on an individual's full genetic profile and family history.
Population Frequency
The frequency of the rs121907987 variant varies significantly across different populations. It is most frequently observed in individuals of Ashkenazi Jewish ancestry, where it is considered a founder mutation. In this population, carrier frequency estimates have historically ranged from approximately 1 in 40 to 1 in 82. In the general global population, the allele frequency is much lower, reported at approximately 0.0005 in databases like gnomAD. Because of its higher prevalence in specific groups, this variant is a standard inclusion in many carrier screening panels designed for individuals of Ashkenazi Jewish descent. These screenings help prospective parents understand their risk of having a child with Canavan disease. If you have received results indicating you are a carrier, it is recommended to discuss the implications with a healthcare provider or a genetic counselor to understand your reproductive options and the nature of autosomal recessive inheritance.
How common is this variant?
The rs121907987 variant has a global allele frequency of approximately 0.0005, but it is significantly more common in individuals of Ashkenazi Jewish ancestry, with carrier frequencies estimated between 1 in 40 and 1 in 82.
Frequently asked questions
What does it mean to be a carrier of the ASPA E285A variant?
Being a carrier means you have one copy of the pathogenic variant and one normal copy of the ASPA gene. Carriers typically do not have symptoms of Canavan disease but can pass the variant to their children.
Is Canavan disease curable?
Currently, there is no cure for Canavan disease. Treatment is primarily supportive, focusing on managing symptoms and improving the quality of life for affected individuals.
Should I get tested for the rs121907987 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 limitations of genetic testing with a doctor or genetic counselor.
If both parents are carriers, what is the risk to their children?
If both parents are carriers of an autosomal recessive condition, there is a 25% chance with each pregnancy that the child will inherit two copies of the variant and be affected by the disease.
Sources & further reading
Educational information only, last refreshed 10/28/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Pathogenic founder mutation (p.Tyr231Ter) associated with Canavan disease.
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.
A nonsense mutation (c.693C>A, p.Tyr231Ter) in ASPA leading to truncated aspartoacylase and defining carrier status for Canavan disease.