ASPA rs121907987: Understanding the E285A Variant
The rs121907987 variant in the ASPA gene is a known pathogenic missense mutation, often referred to as p.Glu285Ala or E285A. It is primarily studied as a carrier marker 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 specific change in the DNA sequence of the ASPA gene. In scientific literature, this is frequently identified as the E285A mutation, where the amino acid glutamic acid is replaced by alanine at position 285 of the aspartoacylase protein. This variant is classified as pathogenic, meaning it is known to disrupt the normal function of the gene. Because Canavan disease is an autosomal recessive condition, an individual typically needs to inherit two copies of a pathogenic variant—one from each parent—to manifest the disease. Carriers, who possess only one copy of this variant, generally do not show symptoms of the condition. This SNP is a focal point in genetic screening panels, particularly for populations where the variant is more prevalent, as identifying carrier status can provide important reproductive health information for families.
The Role of the ASPA Gene
The ASPA gene provides instructions for the body to produce an enzyme called aspartoacylase. This enzyme is essential for the health of the brain, as it breaks down a substance called N-acetylaspartate (NAA). NAA is found in high concentrations in the brain, and its breakdown is necessary for the maintenance of myelin, the protective sheath that covers nerve fibers. When the ASPA gene is mutated, the aspartoacylase enzyme may be absent or non-functional, leading to an accumulation of NAA in the brain. This buildup is toxic to the cells that produce myelin, resulting in a process known as spongy degeneration of the white matter. This disruption of myelin integrity is the hallmark of Canavan disease, which leads to progressive neurological decline, including developmental delays, loss of motor skills, and other severe symptoms.
Research and Clinical Significance
Research into rs121907987 is robust due to its status as a founder mutation in the Ashkenazi Jewish population. Clinical studies have consistently identified this variant as one of the primary causes of Canavan disease. Because of its high frequency in specific groups, it is included in standard carrier screening panels alongside other common mutations like Y231X and A305E. The evidence linking this specific variant to aspartoacylase deficiency is strong, and it is widely recognized by medical genetics organizations. However, it is important to note that while this variant is a major contributor to the disease in certain populations, it is not the only mutation in the ASPA gene that can cause the condition. Genetic testing for this variant is typically used for carrier screening or to confirm a clinical diagnosis in symptomatic individuals.
What You Can Do With This Information
If you have received results regarding the rs121907987 variant, it is essential to understand that this information is for educational purposes and does not constitute a medical diagnosis. If you are concerned about your carrier status or family history, the most appropriate step is to consult with a certified genetic counselor or a medical professional. They can help interpret your results in the context of your overall health and family background. A counselor can also explain the implications of being a carrier, including the potential for passing the variant to offspring and the availability of reproductive options. Never make medical decisions based solely on genetic reports without professional guidance. If you are pregnant or planning a family, discussing these results with your obstetrician or a specialist is the best way to ensure you have accurate information tailored to your specific situation.
How common is this variant?
The carrier frequency for this variant is approximately 1.5% (or 1 in 40 to 1 in 82) in the Ashkenazi Jewish population, while it is significantly rarer in the general global population.
Frequently asked questions
What is Canavan disease?
Canavan disease is a rare, inherited, and progressive neurodegenerative disorder that causes damage to nerve cells in the brain. It is caused by mutations in the ASPA gene, which leads to the accumulation of N-acetylaspartate.
Does having the rs121907987 variant mean I have Canavan disease?
No, being a carrier (having one copy of the variant) does not mean you have the disease. Canavan disease is an autosomal recessive condition, meaning it typically requires two copies of a pathogenic mutation to manifest.
Why is this variant common in Ashkenazi Jewish populations?
This is due to a 'founder effect,' where a specific genetic variant becomes more common in a population because it was present in a small group of ancestors. Over generations, the frequency of this variant remained higher within this specific community.
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 genetic counselor or your healthcare provider.
Sources & further reading
Educational information only, last refreshed 10/12/2026. 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.