GJB2 rs61731363: Understanding This Genetic Variant
The rs61731363 variant is a specific genetic change located within the GJB2 gene, which provides instructions for making the connexin 26 protein. This variant is primarily investigated for its potential role in nonsyndromic sensorineural hearing loss, though its clinical significance remains a subject of ongoing research.
What each genotype means
Typical GJB2 genetic profile
This genotype represents the most common form of the GJB2 gene at this position. It is not associated with the specific hearing loss risks linked to the p.Arg127His variant. Most individuals with this genotype do not have GJB2-related sensorineural hearing loss.
This is the most common genotype found in all major global populations.
Carrier of GJB2 variant
You carry one copy of the p.Arg127His variant. This variant is often classified as having uncertain significance, and carrying a single copy is typically not sufficient to cause recessive GJB2-related hearing loss. You should consult with a genetic counselor to understand if this finding is relevant to your family history.
This genotype is infrequent, occurring in approximately 0.1-0.3% of European and Latino populations.
Homozygous for GJB2 variant
You carry two copies of the p.Arg127His variant. The clinical significance of this homozygous state remains uncertain, as research has yielded mixed results regarding its role in sensorineural hearing loss. It is recommended to discuss these results with an audiologist or genetic specialist to correlate this finding with your clinical hearing status.
This genotype is very rare in the general population.
What is the rs61731363 Variant?
The rs61731363 variant is a single nucleotide polymorphism (SNP) located in the GJB2 gene. In genetic terms, this is classified as a missense variant, meaning the change in the DNA sequence results in a different amino acid being incorporated into the protein structure. Specifically, this variant leads to the substitution of histidine for arginine at position 127 (p.Arg127His) in the resulting connexin 26 protein. Because the GJB2 gene is highly scrutinized for its role in hereditary hearing conditions, researchers track variants like rs61731363 to determine if they alter the function of the protein enough to impact auditory health. It is important to note that identifying a variant does not automatically imply a health outcome, as many genetic changes are benign and do not affect how our bodies function.
The Role of the GJB2 Gene
The GJB2 gene is responsible for producing a protein called connexin 26. This protein is a member of the gap junction family, which acts like a channel between adjacent cells, allowing for the passage of small molecules and ions. In the inner ear, these channels are essential for maintaining the chemical environment necessary for the hair cells to convert sound waves into electrical signals that the brain can interpret. When GJB2 is functioning correctly, it supports the delicate balance of potassium ions required for normal hearing. Mutations in this gene are among the most common genetic causes of nonsyndromic hearing loss, which is hearing loss that occurs without other associated physical symptoms. Because of its critical role, scientists study even rare variants to understand the full spectrum of how GJB2 mutations might disrupt auditory signaling.
Research and Clinical Evidence
The evidence linking rs61731363 to hearing loss is currently classified as limited. While GJB2 is a well-established gene for hearing impairment, the specific impact of the p.Arg127His change is not fully understood. Some studies have reported this variant in individuals with nonsyndromic sensorineural hearing loss, but it is often found in individuals who do not show symptoms or in combination with other genetic factors. In clinical genetics, this variant is frequently categorized as a variant of uncertain significance (VUS). This means that there is not enough conclusive evidence to definitively label it as either benign or pathogenic. Whether this variant contributes to hearing loss may depend on whether an individual carries it on one or both copies of the gene, or if it is present alongside other mutations in the same gene, a state known as compound heterozygosity.
Population Frequency
The rs61731363 variant is considered infrequent in the general population. Data from large-scale genomic databases, such as gnomAD, indicate that the allele frequency for this variant is approximately 0.1% to 0.3% in European and Latino populations. Because the frequency is low, it is not commonly encountered in the general public. The rarity of this variant makes it challenging for researchers to gather enough data to reach a definitive conclusion about its clinical impact. When a variant is this rare, it is difficult to distinguish between a rare benign change and a rare pathogenic one without extensive family studies or functional laboratory testing. Consequently, most individuals who carry this variant do not have a clear clinical diagnosis based on this finding alone.
What This Information Means for You
If you have received information about the rs61731363 variant, it is important to approach it with perspective. Because the evidence for this variant is limited and it is often classified as a variant of uncertain significance, it should not be used as a standalone tool for medical diagnosis. Genetic testing results can be complex, and the presence of a variant does not guarantee that a specific health condition will develop. If you are concerned about hearing health or have a family history of hearing loss, the most appropriate step is to consult with a certified genetic counselor or an audiologist. These professionals can help interpret your results in the context of your personal and family medical history. They can also provide guidance on whether further clinical testing or monitoring is necessary, ensuring that you receive accurate information tailored to your specific situation.
How common is this variant?
The rs61731363 variant is infrequent, with an allele frequency of approximately 0.1-0.3% in European and Latino populations according to gnomAD data.
Frequently asked questions
Is rs61731363 a cause of deafness?
The rs61731363 variant is a variant of uncertain significance, meaning there is not enough evidence to definitively label it as a cause of deafness. While GJB2 mutations are a common cause of hearing loss, this specific variant is not clearly linked to a clinical diagnosis.
What should I do if I have this variant?
If you have this variant, you should not be alarmed, as it is often found in healthy individuals. If you have concerns about your hearing, you should consult with an audiologist or a genetic counselor to discuss your results.
Can I get a test for GJB2 mutations?
Yes, GJB2 testing is available through clinical genetic laboratories, often as part of a panel for hereditary hearing loss. Such tests should be ordered and interpreted by a healthcare professional.
Why is this variant called a VUS?
A variant of uncertain significance (VUS) is a genetic change where the clinical impact is not yet known. Scientists need more data from large populations and functional studies to determine if a VUS is benign or disease-causing.
Sources & further reading
Educational information only, last refreshed 9/24/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Also known as 35delG, this frameshift mutation is a major cause of autosomal recessive nonsyndromic sensorineural hearing loss.
Pathogenic nonsense variant (p.Trp24Ter) in GJB2, representing one of the major causative alleles for autosomal recessive non-syndromic hearing loss in Mediterranean and South Asian groups.
This variant is associated with autosomal recessive nonsyndromic hearing loss.
A missense variant (c.109G>A, p.Val37Ile) in GJB2, often identified as a common pathogenic variant associated with mild to moderate autosomal recessive nonsyndromic hearing loss (DFNB1A).
Frameshift deletion (c.235delC) conferring carrier status for autosomal recessive non-syndromic sensorineural hearing loss.
Common East Asian frameshift mutation (c.235delC) causing severe truncation of Connexin 26, a major cause of autosomal recessive nonsyndromic hearing loss.