The c.110T>C variant in GJB2 is a missense variant predicted to cause substitution of valine by alanine at amino acid 37 (p.Val37Ala). The highest population minor allele frequency in gnomAD v4.1.1 is 0.0337% (25/74924 alleles-African/African American, PM2_Supporting, BA1, and BS1 not met). The computational predictor REVEL yields a score of 0.675 (PP3 not met). This variant has been identified in 11 patients who did not harbor a second variant in GJB2 (PMID 21287563, 17666888, 15365987, GeneDx internal data, Invitae internal data), but has also been detected in two patients in trans with pathogenic/likely pathogenic variants c.167delT (p.Leu56Argfs*26), c.132G>A (p.Trp44Ter) and one predicted in trans with pathogenic/likely pathogenic c.647_650delGATA (p.Arg216Ilefs*17) (2.5 points, PM3_Strong met; Partners Laboratory for Molecular Medicine SCV000967620.2, Molecular Otolaryngology and Renal Research Laboratories internal data). Two different missense variants at this codon (p.Val37Ile ClinVar ID:17023; and p.Val37Phe ClinVar ID:179256) have been classified as pathogenic or likely pathogenic for autosomal recessive non-syndromic HL by the ClinGen HL-VCEP (PM5_Strong met). In summary, based on the current evidence, the variant NM_004004.6(GJB2):c.110T>C (p.Val37Ala) meets the criteria to be classified as pathogenic for autosomal recessive non-syndromic HL based on the ACMG/AMP criteria applied as specified by the ClinGen HL-VCEP: PM3_Strong, PM5_Strong (ClinGen Hearing Loss VCEP specifications version 2; 8/19/2026).