The c.23C>T variant in GJB2 is a missense variant predicted to cause substitution of threonine by methionine at amino acid 8. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0002511 (13/30616 alleles with no homozygotes) in the South Asian population (no population codes met). The computational predictor REVEL gives a score of 0.632, which is neither above nor below the thresholds predicting a damaging or benign impact on GJB2 function. Dual whole cell voltage clamp and dye transfer assays in HeLa cells demonstrated that even though potassium permeability remains the same in the variant, there is a reduction in cationic and large molecules dye transfer compared to WT (PMID:18684989) (PS3_Supporting). This variant has been detected in at least two individuals with autosomal recessive NSHL. One was compound heterozygous for the variant and a pathogenic variant, c.109G>A (p.Val37Ile), with phase unknown (0.5 PM3 points, PMID: 22384008). One individual was homozygous for the variant (0.5 PM3 points, PMID: 31162818) (PM3). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive nonsyndromic genetic hearing loss based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: PM3, PS3_Supporting (Hearing Loss VCEP specifications version 2; 10/31/2022).