HEXA rs397508605: Understanding This Genetic Variant
The rs397508605 variant is a specific genetic change in the HEXA gene that affects how the body processes certain fats. It is recognized as a pathogenic variant associated with carrier status for Tay-Sachs disease, particularly within French Canadian and Cajun populations.
What each genotype means
Typical HEXA gene profile
This genotype indicates you do not carry the specific c.1073+1G>A mutation associated with Tay-Sachs disease. This result does not rule out the presence of other, less common mutations in the HEXA gene that could also affect enzyme function.
This is the most common genotype in all populations worldwide.
Tay-Sachs carrier status
You carry one copy of the c.1073+1G>A mutation, which is a known pathogenic variant linked to Tay-Sachs disease. As an autosomal recessive condition, carriers typically do not show symptoms of the disease, but you should consult with a genetic counselor or physician to discuss reproductive risks and family planning.
This genotype is found at a frequency of up to 0.015 in French Canadian and Cajun populations and is considered rare in most other populations.
Increased risk for Tay-Sachs
This genotype indicates you carry two copies of the c.1073+1G>A mutation. Because this variant is pathogenic and disrupts the function of the HEXA enzyme, individuals with this genotype are at high risk for developing Tay-Sachs disease or related GM2 gangliosidosis. Please consult with a medical specialist or geneticist for clinical evaluation and guidance.
This genotype is extremely rare in the general population.
What is rs397508605?
The variant rs397508605, also identified in clinical literature as c.1073+1G>A, is a single nucleotide change located within the HEXA gene. This gene is situated on chromosome 15. Specifically, this variant occurs at a canonical splice donor site. Splice sites are critical genetic instructions that tell the cell how to correctly assemble the messenger RNA (mRNA) that serves as a blueprint for building proteins. When a mutation occurs at a splice donor site, it can disrupt the normal splicing process, often leading to the production of a non-functional or unstable protein. Because this variant alters a highly conserved nucleotide, it is classified as pathogenic, meaning it is known to interfere with the gene's ability to function as intended.
The Role of the HEXA Gene
The HEXA gene provides instructions for making a protein called the alpha-subunit of the enzyme beta-hexosaminidase A. This enzyme is found in lysosomes, which are the recycling centers of the cell. Its primary job is to break down a fatty substance called GM2 ganglioside. When the HEXA gene is functioning correctly, the enzyme effectively clears these fats from nerve cells in the brain and spinal cord. If the gene contains a pathogenic mutation, the enzyme activity is severely reduced or eliminated. This leads to the toxic accumulation of GM2 ganglioside within cells, which is the underlying mechanism for Tay-Sachs disease. This condition is inherited in an autosomal recessive pattern, meaning an individual must typically inherit two copies of a pathogenic variant to develop the disease.
Research and Clinical Significance
Research into rs397508605 has established its role as a pathogenic variant linked to Tay-Sachs disease. Clinical databases, such as ClinVar, categorize this variant as pathogenic due to its location in a critical splice site and its documented association with loss-of-function in the HEXA enzyme. While Tay-Sachs disease is most famously associated with specific mutations in the Ashkenazi Jewish population, rs397508605 is noted for its presence in other groups. The evidence for this variant is grounded in its impact on protein synthesis. It is important to note that being a carrier of a single pathogenic variant does not mean an individual will develop the disease, as carriers typically have one functional copy of the gene that produces enough enzyme to maintain normal cellular function.
Population Frequency
The frequency of rs397508605 varies significantly by ancestry. While it is considered rare in the general global population, it has been identified at higher frequencies in specific groups, particularly among individuals of French Canadian and Cajun descent. In these populations, the allele frequency has been reported as high as 0.015. This pattern of distribution is often the result of a founder effect, where a genetic variant becomes more common in a population due to the limited number of ancestors who carried the trait. Outside of these specific groups, the variant is observed much less frequently. Understanding these population-specific frequencies is a key component of genetic carrier screening programs, which help individuals understand their reproductive risks.
What This Information Means for You
If you have received information regarding your status for rs397508605, it is essential to understand that this is a carrier status finding. Being a carrier means you possess one copy of the variant, but you do not have the disease. This information is primarily used in the context of family planning and reproductive health. If you are concerned about your genetic status or your risk of passing a variant to your children, the most appropriate step is to consult with a certified genetic counselor or a medical professional. They can provide context based on your personal and family history, explain the implications of carrier status, and discuss testing options for partners. Never use genetic data to make medical decisions without professional guidance.
How common is this variant?
The rs397508605 variant is rare globally but reaches an allele frequency of up to 0.015 in French Canadian and Cajun populations.
Frequently asked questions
What is a carrier of Tay-Sachs disease?
A carrier is an individual who has one copy of a pathogenic mutation in the HEXA gene but does not have the disease. Carriers are typically healthy because their one functional copy of the gene produces enough enzyme to prevent the accumulation of toxic fats.
Is rs397508605 the same as the common Ashkenazi Jewish mutations?
No, rs397508605 is distinct from the three most common mutations found in the Ashkenazi Jewish population. While it also causes Tay-Sachs disease, it is more frequently associated with French Canadian and Cajun ancestry.
Should I be tested for this variant?
Carrier screening is a personal choice often discussed during family planning. If you have a family history of Tay-Sachs disease or belong to a population with a higher carrier frequency, you may wish to speak with a genetic counselor about whether testing is appropriate for you.
What should I do if I am a carrier?
If you are identified as a carrier, it is recommended that you discuss this result with a genetic counselor or your healthcare provider. They can help you understand the implications for your reproductive health and explain the testing options available for your partner.
Sources & further reading
Educational information only, last refreshed 10/14/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Canonical splice junction variant (c.1073+1G>A) causing Tay-Sachs disease.
Pathogenic splice-junction variant (c.1073+1G>A / IVS9+1G>A) causing Tay-Sachs disease when in compound heterozygosity or homozygosity.
Pathogenic splice donor variant (c.1421+1G>C) in HEXA underlying carrier status for autosomal recessive infantile Tay-Sachs disease.
This HEXA variant is associated with Tay-Sachs disease, particularly late-onset forms.
Pathogenic splice junction mutation (c.1421+1G>C) in HEXA leading to Tay-Sachs disease.
A 4-bp insertion (c.1278dupTATC) in HEXA that accounts for over 70% of Tay-Sachs disease alleles in Ashkenazi Jewish carrier screening panels.