GJB2 rs111033237: Understanding the p.Trp24Ter Variant
The rs111033237 variant in the GJB2 gene is a pathogenic nonsense mutation, also known as p.Trp24Ter. It is recognized as a significant genetic factor associated with autosomal recessive non-syndromic hearing loss in Mediterranean and South Asian populations.
What each genotype means
Typical GJB2 function
This genotype represents the common, functional version of the GJB2 gene. Individuals with this profile do not carry the p.Trp24Ter pathogenic variant associated with this specific genetic site.
This is the most common genotype found in the vast majority of the global population.
Carrier of pathogenic variant
You carry one copy of the p.Trp24Ter (W24X) pathogenic variant. Because this condition is inherited in an autosomal recessive pattern, carriers typically do not experience hearing loss, but they may pass the variant to their children.
This genotype is found in approximately 1.6% of certain studied populations, though it varies significantly by ancestry, particularly in South Asian groups.
Increased risk of hearing loss
You carry two copies of the p.Trp24Ter (W24X) pathogenic variant, which results in a premature stop codon and loss of GJB2 protein function. This genotype is strongly associated with autosomal recessive non-syndromic sensorineural hearing loss. Please consult with a clinical geneticist or audiologist to discuss the clinical implications for your hearing health.
This genotype is rare in the general population and is primarily identified in clinical cohorts of individuals with congenital hearing loss.
What is the rs111033237 Variant?
The rs111033237 variant is a specific change in the DNA sequence of the GJB2 gene. In scientific literature, this is often referred to as c.71G>A, which results in a protein-level change known as p.Trp24Ter. This is a 'nonsense' mutation, meaning it introduces a premature stop codon in the genetic instructions. Instead of the cell producing a full-length, functional protein, the process is cut short, leading to a truncated and typically non-functional protein product. This variant is located within the coding region of the GJB2 gene, which is critical for the proper development and function of the inner ear. Because this change disrupts the production of a vital protein, it is classified as pathogenic in clinical databases, meaning it is known to contribute to specific health conditions when inherited in certain patterns.
The Role of the GJB2 Gene
The GJB2 gene provides instructions for making a protein called connexin 26. This protein belongs to a family of gap junction proteins that form channels between adjacent cells, allowing for the passage of small molecules, ions, and electrical signals. In the inner ear, connexin 26 is essential for maintaining the chemical balance of the fluid that surrounds the hair cells, which are the sensory cells responsible for converting sound waves into electrical signals for the brain. When GJB2 is mutated, the resulting dysfunction in these gap junctions can disrupt the homeostasis of the inner ear. This disruption often leads to sensorineural hearing loss, where the inner ear or the nerve pathways from the inner ear to the brain are not functioning correctly. Because this gene is so central to auditory health, variants that cause a loss of function are among the most common genetic causes of congenital hearing loss worldwide.
Research and Clinical Evidence
Research has consistently associated the p.Trp24Ter (rs111033237) variant with autosomal recessive non-syndromic hearing loss. In an autosomal recessive condition, an individual typically needs to inherit two copies of a pathogenic variant—one from each parent—to manifest the hearing loss phenotype. Clinical evidence from databases like ClinVar supports the classification of this variant as pathogenic due to its role in disrupting protein synthesis. While it is a known causative allele, the severity of hearing loss can vary depending on the specific combination of variants an individual carries. It is important to note that genetic testing for GJB2 is widely available and often used in clinical settings to identify the cause of congenital hearing loss. However, the presence of this variant does not guarantee a specific clinical outcome, as other genetic and environmental factors can also influence auditory health.
Population Frequency and Distribution
The frequency of the rs111033237 variant varies significantly across different global populations. It is most frequently observed in Mediterranean and South Asian groups, where it is recognized as a major causative allele for hereditary hearing loss. According to data from the Genome Aggregation Database (gnomAD), the allele frequency in South Asian populations is approximately 0.008. This means that while the variant is present, it is not common in the general population. Because the prevalence of GJB2-related hearing loss and the carrier rate for pathogenic variants are highly population-dependent, genetic screening programs often tailor their approach based on the ancestry of the individual. Understanding these population-specific frequencies is crucial for accurate genetic counseling and for interpreting the significance of test results in a clinical context.
What This Information Means for You
If you or a family member have been identified as a carrier of the rs111033237 variant, it simply means you possess one copy of this specific genetic change. Being a carrier does not typically cause hearing loss, as the condition is recessive. However, if both parents are carriers of a pathogenic GJB2 variant, there is a 25% chance at each conception that a child will inherit two pathogenic variants and potentially experience hearing loss. This information is intended for educational purposes and should not be used for self-diagnosis. If you have concerns about hearing loss or your carrier status, it is essential to consult with a qualified healthcare provider or a genetic counselor. They can provide context based on your personal and family medical history, explain the implications of your results, and discuss appropriate next steps, such as diagnostic testing or clinical evaluation.
How common is this variant?
The rs111033237 variant is most prevalent in Mediterranean and South Asian populations, with a reported allele frequency of approximately 0.008 in South Asian groups according to gnomAD.
Frequently asked questions
Is rs111033237 the only cause of hearing loss?
No, hearing loss is genetically heterogeneous, meaning it can be caused by mutations in many different genes. While GJB2 is a common cause, it is only one of many genes associated with auditory impairment.
What does it mean to be a carrier of a GJB2 variant?
Being a carrier means you have one copy of a pathogenic variant and one normal copy of the gene. Carriers typically do not experience hearing loss themselves but can pass the variant to their children.
Can I be tested for this variant?
Yes, genetic testing for GJB2 is widely available through clinical laboratories. You should discuss the necessity and implications of such testing with a doctor or a genetic counselor.
Does having the A/A genotype guarantee hearing loss?
While the A/A genotype is strongly associated with hearing loss, the clinical expression can be influenced by other genetic and environmental factors. A clinical evaluation by an audiologist or ENT specialist is necessary to assess hearing function.
Sources & further reading
Educational information only, last refreshed 9/27/2026. 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.
This variant is associated with autosomal recessive nonsyndromic hearing loss.
Missense variant (p.Arg127His) in the GJB2 gene. While often reported in individuals with hearing loss, it is frequently classified as benign or likely benign in clinical databases when found in isolation, as it is common in the general population.
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.