SH3TC2 rs80338932: Understanding This Rare Genetic Variant
The rs80338932 variant is a rare genetic finding located within the SH3TC2 gene. It is primarily studied in the context of Charcot-Marie-Tooth disease, a group of inherited conditions that affect the peripheral nerves.
What each genotype means
Typical genetic profile
This is the common, non-pathogenic version of the SH3TC2 gene. It is not associated with the development of Charcot-Marie-Tooth disease type 4C.
This is the most common genotype found in the general population.
Carrier status
This genotype indicates you carry one copy of a variant associated with Charcot-Marie-Tooth disease type 4C. Because this condition is inherited in an autosomal recessive manner, carrying a single copy typically does not cause the disease, though you should consult with a genetic counselor regarding family planning.
This genotype is rare in the general population.
Increased risk profile
This genotype represents the presence of two copies of the variant associated with Charcot-Marie-Tooth disease type 4C. This condition is a recessive peripheral neuropathy characterized by progressive muscle weakness and potential spine deformities; please discuss these findings with a neurologist or medical geneticist for clinical context.
This genotype is very rare and is primarily identified in clinical settings among individuals diagnosed with or suspected of having Charcot-Marie-Tooth disease.
What is rs80338932 and Where is it Located?
The rs80338932 variant is a specific change in the DNA sequence located within the SH3TC2 gene. This gene is situated on chromosome 5 at position 5q32. In genomics, an rsID (reference SNP cluster ID) like rs80338932 acts as a unique identifier for a specific location in the human genome where a single nucleotide polymorphism (SNP) or other small variation may occur. The SH3TC2 gene itself is relatively large, containing 17 exons, and it provides the instructions for building a protein that plays a critical role in the maintenance of peripheral nerves. Because this variant is located within this functional gene, researchers monitor it to see if it alters the protein's structure or the way the gene is expressed. Understanding the exact location of a variant is the first step in determining whether it has a biological impact on human health or if it is simply a neutral piece of genetic variation.
The Role of the SH3TC2 Gene
The SH3TC2 gene encodes a protein known as SH3 domain and tetratricopeptide repeats 2. This protein is primarily expressed in Schwann cells, which are the specialized cells that wrap around peripheral nerves to provide insulation, known as myelin. Myelin is essential for the rapid transmission of electrical signals between the brain and the rest of the body. Research suggests that the SH3TC2 protein acts as an adapter or docking molecule, helping to regulate endocytic recycling and maintaining the integrity of the nodes of Ranvier—the small gaps in the myelin sheath that allow nerve impulses to jump along the axon. When the SH3TC2 protein is dysfunctional, the myelin sheath can degrade, leading to the symptoms associated with peripheral neuropathy. Because of its vital role in nerve health, mutations in this gene are a well-documented focus in the study of hereditary motor and sensory neuropathies.
Research Associations and Evidence Strength
The SH3TC2 gene is famously associated with Charcot-Marie-Tooth disease type 4C (CMT4C), an autosomal recessive condition. This means that for an individual to be affected, they typically must inherit two copies of a pathogenic variant—one from each parent. While many variants in SH3TC2 are linked to this condition, the evidence strength for any single specific variant like rs80338932 can vary significantly. In clinical genetics, a variant is often classified based on its known impact on protein function. Some variants are clearly pathogenic, while others are classified as having 'uncertain significance' if there is not enough data to prove they cause disease. Research into rs80338932 is ongoing, and it is important to distinguish between a variant that is a known cause of disease and one that is merely being investigated for a potential association. Currently, the evidence linking this specific variant to clinical outcomes is considered moderate, requiring careful interpretation by medical professionals.
Population Frequency and Distribution
The rs80338932 variant is classified as rare across most global populations. In large-scale genomic databases like gnomAD, rare variants are often found at very low frequencies, sometimes appearing in only a handful of individuals out of hundreds of thousands. This rarity is common for variants associated with recessive conditions, as they do not typically reach high frequencies in the general population. Because the variant is rare, it is difficult to establish strong statistical associations with specific health traits without large, diverse cohorts. The distribution of such variants can also be influenced by ancestry, with some rare variants appearing more frequently in specific geographic or ethnic groups due to founder effects. Researchers continue to collect data to better understand how common this variant is across different ancestral backgrounds, which helps in determining its overall impact on human health.
What You Can and Cannot Do With This Information
Genetic information regarding variants like rs80338932 is intended for educational purposes and should not be used for self-diagnosis. If you have received a report mentioning this variant, it is important to remember that a single genetic finding does not determine your health status. Many factors, including other genes and environmental influences, contribute to the development of complex conditions like peripheral neuropathy. You cannot use this information to make medical decisions, such as starting or stopping treatments. If you are concerned about your genetic results or a family history of nerve-related conditions, the most appropriate step is to consult with a board-certified genetic counselor or a neurologist. These professionals can provide context, explain the limitations of current research, and help you understand what, if any, clinical follow-up is necessary based on your personal and family medical history.
How common is this variant?
The rs80338932 variant is considered rare, with a low allele frequency observed across most global populations in genomic databases.
Frequently asked questions
Is rs80338932 a cause of Charcot-Marie-Tooth disease?
The SH3TC2 gene is associated with Charcot-Marie-Tooth disease type 4C, but not every variant in the gene causes the condition. The clinical significance of rs80338932 should be evaluated by a medical professional based on your specific genetic report.
What should I do if I have the rs80338932 variant?
If you have this variant, do not panic, as many rare variants have no known clinical impact. You should discuss the finding with a genetic counselor or your primary care physician to understand its relevance to your health.
Is this variant inherited?
Yes, like all genetic variants, rs80338932 is inherited from your parents. It follows standard patterns of inheritance, and its presence in your genome is determined at conception.
Can I get tested for this variant?
Yes, this variant can be identified through clinical genetic testing or research-based sequencing. However, testing should always be performed in a certified laboratory and interpreted by a qualified healthcare provider.
Sources & further reading
Educational information only, last refreshed 9/25/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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