GJB2 rs111033622: Understanding the c.235delC Variant
The rs111033622 variant, commonly known as c.235delC, is a genetic alteration in the GJB2 gene. It is primarily recognized as a carrier status marker associated with autosomal recessive nonsyndromic hearing loss, particularly within East Asian populations.
What each genotype means
Typical GJB2 profile
This genotype represents the absence of the c.235delC variant. Individuals with this profile do not carry this specific genetic risk factor for GJB2-related nonsyndromic hearing loss.
This is the most common genotype, found in the vast majority of the global population.
GJB2 carrier status
You carry one copy of the c.235delC variant, also known as p.Leu79CysfsTer3. This is a common frameshift mutation in East Asian populations associated with autosomal recessive nonsyndromic hearing loss, meaning that while you are a carrier, you typically do not experience hearing loss yourself unless you also carry a second pathogenic mutation on the other copy of the gene.
Carried by approximately 1% to 1.6% of individuals in East Asian populations.
GJB2-related hearing loss risk
You carry two copies of the c.235delC variant. This genotype is associated with autosomal recessive nonsyndromic hearing loss, though the severity can be highly heterogeneous, ranging from profound congenital deafness to post-lingual or mild-to-moderate hearing impairment. Please consult with an audiologist or genetic counselor to discuss your specific hearing health and clinical context.
This genotype is rare in the general population, occurring primarily in individuals of East Asian ancestry.
What is the rs111033622 Variant?
The rs111033622 variant is a specific genetic change located within the GJB2 gene on chromosome 13. In scientific literature, this variant is frequently referred to as c.235delC, which describes a frameshift deletion of a single cytosine nucleotide. This deletion causes a shift in the reading frame of the genetic code, leading to a premature termination codon and a severely truncated, non-functional protein. Because this variant is located in a gene critical for auditory function, it has been extensively studied as a primary target for genetic screening. It is important to note that this variant is a recessive marker, meaning that an individual typically needs to inherit the variant from both parents to manifest the associated hearing loss phenotype. As a carrier, an individual possesses one copy of the variant and one functional copy, which generally does not result in hearing loss.
The Role of the GJB2 Gene
The GJB2 gene provides instructions for creating a protein called connexin 26. This protein is a member of the gap-junction family, which acts as a channel between adjacent cells, allowing for the exchange of ions, nutrients, and signaling molecules. In the inner ear, connexin 26 is essential for maintaining the chemical environment necessary for the hair cells to function properly. These hair cells are responsible for converting sound vibrations into electrical signals that the brain interprets as sound. When GJB2 mutations occur, the resulting connexin 26 protein may be absent or dysfunctional, disrupting the homeostasis of the cochlea. This disruption prevents the efficient transmission of signals, which is the underlying mechanism for the nonsyndromic hearing loss associated with this gene. Because this process is vital for hearing, GJB2 is considered one of the most significant genes involved in hereditary deafness.
Research and Clinical Evidence
Research into rs111033622 has established it as a major pathogenic variant for nonsyndromic hearing loss, especially in East Asian populations. Studies have consistently identified this specific deletion as a leading cause of autosomal recessive hearing loss in countries such as China and Japan. While the evidence linking this variant to hearing loss is strong, the clinical presentation can vary. Genetic testing for this variant is often included in panels for individuals with a family history of hearing loss or those seeking carrier screening. However, the evidence strength for this variant is sometimes categorized as limited in broader, global contexts because its prevalence and clinical impact are highly ancestry-specific. It is essential to understand that genetic testing results should always be interpreted by a qualified genetic counselor or medical professional who can provide context based on an individual's specific family history and clinical presentation.
Population Frequency
The frequency of the rs111033622 variant is notably higher in East Asian cohorts, where it is estimated to have a carrier frequency of approximately 0.012. This makes it a significant focus for regional genetic health initiatives. In contrast, this specific deletion is much less common or absent in many other global populations, where different GJB2 variants, such as c.35delG, may be more prevalent. The variation in frequency highlights the importance of considering ancestral background when interpreting genetic screening results. Because the variant is relatively common in specific regions, it is frequently included in standard carrier screening panels for those populations. Understanding these population-specific frequencies helps researchers and clinicians better assess the likelihood of an individual being a carrier and the potential risk for offspring in the context of autosomal recessive inheritance patterns.
Managing Your Genetic Information
If you have received information regarding your status for the rs111033622 variant, it is important to approach the data with a clear understanding of its limitations. This information is intended for educational purposes and does not constitute a medical diagnosis. A carrier status result simply indicates that you carry one copy of the variant, which is generally not associated with hearing loss in the carrier themselves. If you are concerned about the risk of passing this variant to children, the most appropriate step is to consult with a genetic counselor. They can help you understand the inheritance patterns, the probability of passing the variant to offspring, and the implications for family planning. Never make medical decisions based solely on genetic reports without professional guidance. Your healthcare provider can help you navigate the complexities of genetic testing and determine if further clinical evaluation or testing for your partner is necessary.
How common is this variant?
The rs111033622 variant has a reported frequency of approximately 0.012 in East Asian cohorts, making it a common target for carrier testing in that population.
Frequently asked questions
What does it mean to be a carrier of GJB2?
Being a carrier means you have one copy of a GJB2 variant and one functional copy. Carriers typically do not experience hearing loss themselves, but they can pass the variant to their children.
Is the rs111033622 variant the only cause of hearing loss?
No, hearing loss is genetically heterogeneous, meaning it can be caused by many different genes and variants. GJB2 is just one of many genes associated with nonsyndromic hearing loss.
Should I get tested for this variant?
Genetic testing is a personal decision often made in consultation with a healthcare provider. It is typically considered if there is a family history of hearing loss or for reproductive planning.
Can this variant be treated?
There is currently no cure for genetic hearing loss caused by GJB2 mutations. Management typically involves audiological support, such as hearing aids or cochlear implants, to assist with communication.
Sources & further reading
Educational information only, last refreshed 9/23/2026. 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.
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.