GJB2 rs111033399: What Your Genotype Means
The rs111033399 variant is a single-nucleotide change located in the GJB2 gene, commonly designated in clinical genetics as c.109G>A (p.Val37Ile). It is established as a hypomorphic, pathogenic allele linked to autosomal recessive nonsyndromic hearing impairment 1A (DFNB1A). Because the variant displays incomplete penetrance and variable expressivity, having one or even two copies does not guarantee hearing loss.
What each genotype means
Typical hearing loss risk
You have two reference copies of the GJB2 gene and do not carry the c.109G>A (p.Val37Ile) variant. This genotype is not associated with GJB2-related autosomal recessive non-syndromic hearing loss. It does not rule out hearing impairment from other genetic or environmental causes.
Carried by over 99% of European and African individuals, and by approximately 85% to 86% of individuals of East Asian ancestry.
Carrier of GJB2 variant
You carry one copy of the c.109G>A variant, meaning you are an asymptomatic carrier for autosomal recessive non-syndromic hearing loss 1A. Carriers typically maintain normal hearing but can pass the variant to offspring. If a partner also carries a pathogenic GJB2 variant, future children have an increased likelihood of inheriting biallelic changes.
Found in about 13% to 15% of individuals of East Asian descent, but occurs in well under 1% of European and African populations.
Increased risk of hearing loss
You have two copies of the c.109G>A variant, a genotype associated with an elevated likelihood of mild-to-moderate sensorineural hearing impairment. The variant displays incomplete penetrance and variable expressivity, meaning that while some individuals develop progressive or late-onset hearing loss, others retain normal hearing. Routine hearing assessments can help monitor auditory function over time.
Carried by approximately 0.5% to 1.0% of individuals of East Asian ancestry; it is exceptionally rare in other global ancestries.
Understanding rs111033399 and the GJB2 Gene
The rs111033399 variant represents a point mutation (c.109G>A) within exon 2 of the GJB2 gene, situated on chromosome 13q12.11. This single-base substitution replaces the amino acid valine with isoleucine at codon 37 (p.Val37Ile). The GJB2 gene encodes gap junction protein beta 2, also known as connexin 26 (Cx26). Connexin 26 subunits assemble into hexameric hemichannels that dock with adjacent cells in the inner ear to form gap junctions. These microscopic tunnels are vital for cochlear physiology, allowing the rapid recycling of potassium ions back to the endolymph following sensory hair cell depolarization. Disruptions in this cellular communication pathway prevent the cochlea from maintaining the endocochlear potential necessary for hearing.
Clinical Significance and Disease Association
Historically debated due to its presence in healthy control individuals, rs111033399 has been re-evaluated by the ClinGen Hearing Loss Expert Panel as a pathogenic variant with incomplete penetrance and variable expressivity. Autosomal recessive nonsyndromic hearing impairment 1A typically manifests when an individual inherits two pathogenic GJB2 alleles—either homozygous p.Val37Ile or compound heterozygous alongside another pathogenic change, such as c.235delC or c.35delG. Individuals carrying two causative alleles often present with mild-to-moderate, bilateral, sensorineural hearing loss that may be prelingual or develop later in childhood. Penetrance is estimated to be relatively low in homozygotes, meaning a significant proportion of biallelic individuals maintain normal hearing throughout childhood, while others may experience subtle, progressive auditory shifts.
Ancestry and Population Distribution
The rs111033399 variant exhibits marked population stratification, with its highest frequencies reported across East and Southeast Asian communities. In cohorts of Chinese Han, Vietnamese, Thai, Japanese, and Korean ancestry, the minor A allele typically reaches frequencies between 0.04 and 0.08, with carrier frequencies exceeding 8% to 10% in some regional studies. In contrast, the variant is exceptionally rare in individuals of European, African, and Indigenous American ancestries, where other GJB2 disruptions like c.35delG are more prevalent. Because it reaches polymorphic frequencies in East Asia, interpreting its clinical meaning requires careful evaluation alongside family history, personal audiograms, and broader population genomics databases.
What to Do With Your Genetic Results
Identifying an rs111033399 allele through consumer testing indicates carrier status or, if two copies are identified, genetic susceptibility to recessive hearing changes. Because it is inherited in an autosomal recessive pattern, a single copy does not cause hearing impairment; carriers are typically asymptomatic but could pass the variant to offspring. If you carry this allele, a board-certified genetic counselor or otolaryngologist can provide comprehensive reproductive counseling and review partner testing options. For individuals found to carry two variants (either homozygous AA or compound heterozygous with another GJB2 variant), regular pediatric or adult audiometric evaluations are recommended to monitor auditory thresholds, ensuring early intervention if progressive hearing changes arise.
How common is this variant?
The minor A allele occurs at an allele frequency of approximately 0.06 to 0.08 in East Asian populations, resulting in a carrier rate of 8% to 10%, while it is extremely rare among European and African cohorts.
Frequently asked questions
Does having the rs111033399 variant mean I will go deaf?
No. Carrying a single copy makes you a carrier with typical hearing, and even individuals with two copies often experience only mild-to-moderate hearing impairment or normal hearing due to incomplete penetrance.
How is rs111033399 inherited?
It is inherited in an autosomal recessive manner. An individual must typically inherit a pathogenic GJB2 variant from both parents to be at clinical risk for associated hearing impairment.
Why is this variant so common in East Asian populations?
Population genetic studies indicate an ancient founder effect that led the c.109G>A allele to become prevalent across East and Southeast Asian lineages while remaining very rare in other world regions.
Can routine newborn hearing screening detect issues related to rs111033399?
Not always. Because rs111033399 frequently associates with mild, high-frequency, or later-onset hearing loss, affected newborns can pass standard infant auditory screening tests.
Sources & further reading
Educational information only, last refreshed 9/12/2026. 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.