GJB2 (Gap junction beta-2 protein) variants and mutations
GJB2 (also known as Gap junction beta-2 protein) is a human protein-coding gene encoding a gap junction beta-2 protein. Its connexin 26 channels support potassium and metabolite recycling within the cochlea and communication across epithelial gap junctions. Biallelic pathogenic variants are among the most common causes of congenital nonsyndromic hearing loss, while dominant variants can cause syndromic deafness with skin disease. This analysis covers 681 GJB2 variants and mutations. Of these, 93% have computational variant effect predictions. Disease context includes palmoplantar keratoderma-deafness syndrome, autosomal dominant nonsyndromic hearing loss 3A, and keratoderma hereditarium mutilans. Example GJB2 variants include M1I, M1L, and M1R.
Variant analysis overview
- Gene: GJB2
- Protein: Gap junction beta-2 protein
- UniProt accession: P29033
- Organism: Homo sapiens
- Variants analyzed: 681
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 445 unspecified-consequence records; 1 stop retained variant; 1 stop lost; 111 synonymous variants; 46 frameshift variants; 7 stop-gained variants; 60 missense variants; 6 in-frame deletions; 1 in-frame insertions; 1 protein altering variant; 2 substitution
- Prediction scores: 634 variants have prediction scores (93% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: palmoplantar keratoderma-deafness syndrome, autosomal dominant nonsyndromic hearing loss 3A, keratoderma hereditarium mutilans, Bart-Pumphrey syndrome, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, KID syndrome, Knuckle pads-leukonychia-sensorineural deafness-palmoplantar hyperkeratosis synd, autosomal recessive nonsyndromic hearing loss 1A, hearing loss disorder, deafness, hearing loss, autosomal recessive, nonsyndromic genetic hearing loss.
Protein structure and variant hotspots
- Protein features: 4 transmembrane segments; 3 binding sites.
- Structural context: 245 variants have structural context.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable GJB2 variants
Examples include M1I, M1L, M1R, M1T, M1V, D2N, W3*, W3C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs2500253846, ClinGen CA387462302, ClinVar RCV002966866, ClinVar RCV003315266, Pathogenic, Nonsyndromic genetic hearing loss
- M1L (p.Met1Leu), rs111033293, ClinGen CA387462311, ClinVar RCV000665536, ClinVar RCV003660822, MetaLR 0.92, MetaSVM 1.04, Likely pathogenic, Nonsyndromic genetic hearing loss
- M1R (p.Met1Arg), rs371086981, ClinGen CA387462304, ClinVar RCV000667085, ClinVar RCV003688870, MetaLR 0.95, MetaSVM 1.10, Pathogenic, Nonsyndromic genetic hearing loss
- M1T (p.Met1Thr), rs371086981, ClinGen CA6904336, ClinVar RCV000409687, ClinVar RCV000410366, MetaLR 0.95, MetaSVM 1.10, Pathogenic, Nonsyndromic genetic hearing loss
- M1V (p.Met1Val), rs111033293, ClinGen CA198806, ClinVar RCV000037821, ClinVar RCV000211762, MetaLR 0.92, MetaSVM 1.04, Pathogenic, Nonsyndromic genetic hearing loss
- D2N (p.Asp2Asn), NCI-TCGA Cosmic COSV1012, cosmic curated COSV10124, REVEL 0.51, MetaLR 0.88, Variant assessed as somatic; moderate impact.
- W3* (p.Trp3Ter), rs111033401, ClinGen CA261655, ClinVar RCV000037874, ClinVar RCV000666282, AlphaMissense 0.99, MetaLR 0.99, Pathogenic
- W3C (p.Trp3Cys), rs111033401, ClinGen CA387462278, ClinVar RCV001280637, ClinVar RCV001664795, AlphaMissense 0.99, MetaLR 0.99, Uncertain significance, not specified; not provided
- W3S (p.Trp3Ser), rs2500253823, ClinGen CA387462281, ClinVar RCV003321350, Uncertain significance, not provided
- G4D (p.Gly4Asp), rs111033222, ClinGen CA134947, ClinVar RCV000037814, ClinVar RCV000290549, REVEL 0.36, MetaLR 0.90, Conflicting interpretations, not specified; not provided; Ichthyosis, hystrix-like, with hearing loss
- G4S (p.Gly4Ser), TOPMed rs1959063951, gnomAD rs1959063951, REVEL 0.36, MetaLR 0.78
- G4V (p.Gly4Val), 1000Genomes rs111033222, ESP rs111033222, ExAC rs111033222, TOPMed rs111033222, REVEL 0.40, MetaLR 0.92, Benign
- G4A (p.Gly4Ala), rs1555342014, gnomAD 13-20189570-GC-G, CADD 22.30
- T5M (p.Thr5Met), rs781085903, ClinGen CA6904334, cosmic curated COSV10749, ClinVar RCV000711345, REVEL 0.47, MetaLR 0.94, Uncertain significance, Mutilating keratoderma; Palmoplantar keratoderma-deafness syndrome; Knuckle pads
- T5T (p.Thr5Thr), rs757226502, gnomAD 13-20189567-C-G, CADD 0.02
- L6L (p.Leu6Leu), gnomAD 13-20189564-C-A, CADD 0.41
- Q7* (p.Gln7Ter), rs111033451, ClinGen CA261641, ClinVar RCV000037820, ClinVar RCV000211718, CADD 37.00, Pathogenic
- Q7Q (p.Gln7Gln), rs137932057, gnomAD 13-20189561-C-T, CADD 0.54
- Q7P (p.Gln7Pro), gnomAD 13-20189562-T-G, REVEL 0.73, MetaLR 0.94
- T8M (p.Thr8Met), rs529500747, ClinGen CA6904332, cosmic curated COSV67010, ClinVar RCV000429597, REVEL 0.63, MetaLR 0.91, Uncertain significance, Nonsyndromic genetic hearing loss
- T8T (p.Thr8Thr), gnomAD 13-20189558-C-A, CADD 0.09
- I9V (p.Ile9Val), NCI-TCGA Cosmic COSV1012, cosmic curated COSV10124, REVEL 0.38, MetaLR 0.80, Variant assessed as somatic; moderate impact.
- I9I (p.Ile9Ile), rs1286249617, gnomAD 13-20189555-G-T, CADD 4.05
- I9T (p.Ile9Thr), gnomAD 13-20189556-A-G, REVEL 0.72, MetaLR 0.93
- I9N (p.Ile9Asn), gnomAD 13-20189556-A-T, REVEL 0.76, MetaLR 0.93
- L10M (p.Leu10Met), NCI-TCGA Cosmic COSV6701, cosmic curated COSV67010, Variant assessed as somatic; moderate impact.
- L10P (p.Leu10Pro), rs1959063711, ClinGen CA387462233, ClinVar RCV001257046, Ensembl rs1959063711, AlphaMissense 0.98, MetaLR 0.99, Uncertain significance, Nonsyndromic genetic hearing loss
- L10L (p.Leu10Leu), rs1215210213, gnomAD 13-20189552-C-G, CADD 2.42
- L10W (p.Leu10Trp), rs1441862662, gnomAD 13-20189553-AG-A, CADD 21.50
- G11R (p.Gly11Arg), NCI-TCGA Cosmic COSV6701, cosmic curated COSV67010, Variant assessed as somatic; moderate impact.
- G11L (p.Gly11Leu), rs397516873, gnomAD 13-20189513-GATCT, CADD 31.00
- G11A (p.Gly11Ala), rs1290698257, gnomAD 13-20189536-GTTTG, CADD 27.80
- G11G (p.Gly11Gly), rs753943758, gnomAD 13-20189549-C-A, CADD 1.92
- G12C (p.Gly12Cys), rs104894408, ClinGen CA172224, ClinVar RCV000037839, ClinVar RCV000080371, REVEL 0.84, AlphaMissense 0.86, Likely pathogenic, Nonsyndromic genetic hearing loss
- G12D (p.Gly12Asp), rs1801002, ClinGen CA6904330, cosmic curated COSV10749, ClinVar RCV000666230, REVEL 0.88, MetaLR 0.97, Conflicting interpretations, Autosomal recessive nonsyndromic hearing loss 1A; not provided; not specified
- G12R (p.Gly12Arg), rs104894408, ClinGen CA127028, ClinVar RCV000018548, UniProt VAR 015453, AlphaMissense 0.86, MetaLR 0.96, Likely pathogenic, Autosomal recessive nonsyndromic hearing loss 1A
- G12V (p.Gly12Val), rs1801002, ClinGen CA172228, ClinVar RCV000020570, ClinVar RCV000146020, REVEL 0.95, MetaLR 0.98, Pathogenic/Likely pathogenic, Rare genetic deafness; Knuckle pads, deafness AND leukonychia syndrome; Mutilati
- G12G (p.Gly12Gly), gnomAD 13-20189546-A-G, CADD 6.58
- V13G (p.Val13Gly), rs1593351795, ClinGen CA387462207, ClinVar RCV001001343, Ensembl rs1593351795, AlphaMissense 0.72, MetaLR 0.98, Uncertain significance, not specified
- V13M (p.Val13Met), rs768130937, ClinGen CA6904329, ClinVar RCV000779131, ClinVar RCV001112644, REVEL 0.93, MetaLR 0.99, Conflicting interpretations, Ichthyosis, hystrix-like, with hearing loss; not specified; Autosomal recessive
- V13V (p.Val13Val), rs1415433002, gnomAD 13-20189543-C-T, CADD 5.91
- V13C (p.Val13Cys), rs80338939, gnomAD 13-20189546-A-AC, CADD 25.50
- N14D (p.Asn14Asp), rs1476034902, ClinGen CA387462206, ClinVar RCV001204537, ClinVar RCV004768913, REVEL 0.87, MetaLR 0.97, Pathogenic/Likely pathogenic, not provided; Autosomal recessive nonsyndromic hearing loss 1A
- N14S (p.Asn14Ser), rs2137308851, ClinGen CA387462199, ClinVar RCV003063623, Ensembl rs2137308851, REVEL 0.75, MetaLR 0.94, Likely pathogenic, not provided
- N14K (p.Asn14Lys), rs1165937383, gnomAD 13-20189540-G-GT, CADD 26.60
- N14N (p.Asn14Asn), rs1454922285, gnomAD 13-20189540-G-A, CADD 3.73
- K15T (p.Lys15Thr), rs111033217, ClinGen CA261649, ClinVar RCV000037855, ClinVar RCV000211780, REVEL 0.73, MetaLR 0.92, Pathogenic/Likely pathogenic, Rare genetic deafness; Mutilating keratoderma; Ichthyosis, hystrix-like, with he
- H16N (p.His16Asn), cosmic curated COSV67010
- H16Q (p.His16Gln), cosmic curated COSV10124, MetaLR 0.97, MetaSVM 1.11
- H16Y (p.His16Tyr), ExAC rs762466001, REVEL 0.39, MetaLR 0.87
- H16P (p.His16Pro), gnomAD 13-20189531-GGAGT, CADD 31.00
- H16H (p.His16His), rs1325665848, gnomAD 13-20189534-G-A, CADD 9.81
- S17C (p.Ser17Cys), rs28929485, ClinGen CA185218, ClinVar RCV000156624, Ensembl rs28929485, AlphaMissense 0.99, MetaLR 0.99, Uncertain significance, not specified
- S17F (p.Ser17Phe), rs28929485, ClinGen CA127029, ClinVar RCV000018549, UniProt VAR 015454, AlphaMissense 0.99, MetaLR 0.99, Pathogenic, Autosomal recessive nonsyndromic hearing loss 1A
- S17Y (p.Ser17Tyr), cosmic curated COSV10124, MetaLR 0.99, MetaSVM 1.02
- T18S (p.Thr18Ser), rs1566529035, ClinGen CA387462150, ClinVar RCV000711352, Ensembl rs1566529035, AlphaMissense 0.80, MetaLR 0.98, Uncertain significance, not provided
- T18L (p.Thr18Leu), gnomAD 13-20189524-TGCTG, CADD 32.00
- T18T (p.Thr18Thr), gnomAD 13-20189528-G-C, CADD 10.30
- S19I (p.Ser19Ile), rs2500253355, ClinGen CA2825002101, ClinVar RCV004526452, REVEL 0.82, MetaLR 0.95, Uncertain significance, not specified
- S19T (p.Ser19Thr), rs80338941, ClinGen CA342005, cosmic curated COSV67010, ClinVar RCV000020575, REVEL 0.63, MetaLR 0.94, Pathogenic, Nonsyndromic genetic hearing loss
- I20M (p.Ile20Met), rs749693224, ClinGen CA6904326, ClinVar RCV000505534, ClinVar RCV001857232, REVEL 0.60, MetaLR 0.93, Pathogenic/Likely pathogenic, Ichthyosis, hystrix-like, with hearing loss; Autosomal recessive nonsyndromic he
- I20T (p.Ile20Thr), rs1057517519, ClinGen CA16041595, ClinVar RCV000410601, ClinVar RCV000411693, REVEL 0.93, MetaLR 0.97, Pathogenic, Nonsyndromic genetic hearing loss; not provided; Autosomal recessive nonsyndromi
- I20K (p.Ile20Lys), gnomAD 13-20189519-TCCAA, CADD 29.50
- G21E (p.Gly21Glu), cosmic curated COSV67010, Ensembl rs1311553564
- G21R (p.Gly21Arg), Ensembl rs2137308800
- K22N (p.Lys22Asn), rs879253741, ClinGen CA10584002, ClinVar RCV000234850, Ensembl rs879253741, AlphaMissense 0.97, MetaLR 0.97, Pathogenic, Palmoplantar keratoderma-deafness syndrome
- K22K (p.Lys22Lys), rs879253741, gnomAD 13-20189516-C-T, AlphaMissense 0.97, MetaLR 0.97
- I23M (p.Ile23Met), Ensembl rs1566529011, REVEL 0.81, MetaLR 0.97
- I23T (p.Ile23Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- W24* (p.Trp24Ter), rs769486081, ClinGen CA387462076, ClinVar RCV000670427, ClinVar RCV002531252, CADD 41.00, Pathogenic
- W24C (p.Trp24Cys), ExAC rs769486081, TOPMed rs769486081, MetaLR 0.99, MetaSVM 1.01, Likely pathogenic, Autosomal recessive nonsyndromic hearing loss 1A
- W24S (p.Trp24Ser), gnomAD 13-20189511-C-G, REVEL 0.91, MetaLR 0.99
- L25F (p.Leu25Phe), rs1555342006, ClinGen CA387462069, ClinVar RCV000522480, Ensembl rs1555342006, AlphaMissense 0.83, MetaLR 0.98, Uncertain significance, not provided
- L25P (p.Leu25Pro), NCI-TCGA Cosmic COSV6701, cosmic curated COSV67010, Variant assessed as somatic; moderate impact.
- T26A (p.Thr26Ala), Ensembl rs2137308763, REVEL 0.60, MetaLR 0.92
- T26I (p.Thr26Ile), cosmic curated COSV10124, TOPMed rs1293599962, gnomAD rs1293599962, REVEL 0.71, MetaLR 0.95
- T26T (p.Thr26Thr), rs201848820, gnomAD 13-20189504-G-A, CADD 0.41
- V27I (p.Val27Ile), rs2274084, ClinGen CA134997, cosmic curated COSV67010, ClinVar RCV000029942, REVEL 0.57, MetaLR 0.00, Benign/Likely benign, not specified
- V27V (p.Val27Val), gnomAD 13-20189501-G-C, CADD 5.97
- L28F (p.Leu28Phe), cosmic curated COSV10470
- L28V (p.Leu28Val), rs2500253148, ClinGen CA387462043, ClinVar RCV003699682, Likely pathogenic, not provided
- I30F (p.Ile30Phe), rs374625633, ClinGen CA387462020, ClinVar RCV002812017, AlphaMissense 0.20, MetaLR 0.93, Pathogenic, not provided
- I30T (p.Ile30Thr), rs2500253112, ClinGen CA387462017, ClinVar RCV003573586, Likely pathogenic, not provided
- I30V (p.Ile30Val), rs374625633, ClinGen CA6904323, ClinVar RCV000672312, ClinVar RCV002298731, REVEL 0.70, AlphaMissense 0.20, Uncertain significance, not specified; Autosomal dominant nonsyndromic hearing loss 3A; X-linked mixed h
- R32C (p.Arg32Cys), rs371024165, ClinGen CA273921, cosmic curated COSV67010, ClinVar RCV000169075, REVEL 0.91, MetaLR 0.99, Pathogenic, Rare genetic deafness; Monogenic hearing loss; Palmoplantar keratoderma-deafness
- R32H (p.Arg32His), rs111033190, ClinGen CA261654, ClinVar RCV000037873, ClinVar RCV000410025, REVEL 0.95, MetaLR 0.99, Pathogenic, Monogenic hearing loss; GJB2-related disorder; Rare genetic deafness
- R32L (p.Arg32Leu), rs111033190, ClinGen CA6904322, ClinVar RCV000597784, ClinVar RCV000678865, REVEL 0.98, MetaLR 0.99, Pathogenic/Likely pathogenic, Autosomal dominant keratitis-ichthyosis-hearing loss syndrome; Knuckle pads, dea
- R32P (p.Arg32Pro), ExAC rs111033190, TOPMed rs111033190, gnomAD rs111033190, MetaLR 0.99, MetaSVM 0.96, Conflicting interpretations, not provided; not specified
- R32S (p.Arg32Ser), rs371024165, ClinGen CA387461995, ClinVar RCV000664869, ClinVar RCV000762905, REVEL 0.98, MetaLR 0.99, Pathogenic, Autosomal recessive nonsyndromic hearing loss 1A; Mutilating keratoderma; Ichthy
- R32A (p.Arg32Ala), rs1959062825, gnomAD 13-20189488-GA-G, CADD 22.70
- I33T (p.Ile33Thr), rs575453513, ClinGen CA246460935, ClinVar RCV003062565, ClinVar RCV004690348, REVEL 0.94, MetaLR 0.98, Pathogenic/Likely pathogenic, Monogenic hearing loss; Ichthyosis, hystrix-like, with hearing loss; Autosomal d
- I33I (p.Ile33Ile), gnomAD 13-20189483-A-T, CADD 6.07
- M34L (p.Met34Leu), rs564084861, ClinGen CA6904321, ClinVar RCV000991846, ClinVar RCV001271884, REVEL 0.61, MetaLR 0.80, Uncertain significance, not specified; not provided
- M34R (p.Met34Arg), rs35887622, ClinGen CA261633, ClinVar RCV000037811, ClinVar RCV001731332, AlphaMissense 0.44, MetaLR 0.84, Conflicting interpretations, not specified; not provided
- M34T (p.Met34Thr), rs35887622, ClinGen CA172206, ClinVar RCV000018523, ClinVar RCV000080364, REVEL 0.70, AlphaMissense 0.44, Pathogenic, Nonsyndromic genetic hearing loss
- p.Met34 Ile35del, rs751509573, gnomAD 13-20189477-GATCA, CADD 18.40
- M34* (p.Met34Ter), rs1566528961, gnomAD 13-20189482-TA-T, CADD 21.80
- I35S (p.Ile35Ser), rs756467247, ClinGen CA6904320, ClinVar RCV001544685, ClinVar RCV003331179, REVEL 0.97, MetaLR 0.98, Pathogenic/Likely pathogenic, Nonsyndromic genetic hearing loss; not provided
- I35V (p.Ile35Val), cosmic curated COSV10124, MetaLR 0.96, MetaSVM 1.08
- L36F (p.Leu36Phe), NCI-TCGA Cosmic COSV6701, cosmic curated COSV67010, Variant assessed as somatic; moderate impact.
- L36P (p.Leu36Pro), rs587783644, ClinGen CA172208, ClinVar RCV000146004, ClinVar RCV000518385, REVEL 0.94, MetaLR 0.98, Uncertain significance, Nonsyndromic genetic hearing loss
- L36L (p.Leu36Leu), rs138547875, gnomAD 13-20189474-G-C, CADD 0.05
- V37A (p.Val37Ala), rs141774369, ClinGen CA6904317, cosmic curated COSV67010, ClinVar RCV000520583, REVEL 0.68, MetaLR 0.95, Likely pathogenic, Nonsyndromic genetic hearing loss
- V37F (p.Val37Phe), rs72474224, ClinGen CA273605, ClinVar RCV000156043, ClinVar RCV001850145, AlphaMissense 0.16, MetaLR 0.89, Likely pathogenic, Rare genetic deafness; not provided
- V37I (p.Val37Ile), rs72474224, ClinGen CA172210, cosmic curated COSV10972, ClinVar RCV000018550, REVEL 0.66, AlphaMissense 0.16, Pathogenic, Nonsyndromic genetic hearing loss
- V38L (p.Val38Leu), gnomAD 13-20189470-C-G, REVEL 0.50, MetaLR 0.91
- A40E (p.Ala40Glu), rs111033296, ClinGen CA261635, ClinVar RCV000037813, ClinVar RCV001090238, REVEL 0.96, AlphaMissense 0.53, Pathogenic/Likely pathogenic, Rare genetic deafness; Nonsyndromic genetic hearing loss; not provided
- A40G (p.Ala40Gly), rs111033296, ClinGen CA274135, ClinVar RCV000169292, ESP rs111033296, AlphaMissense 0.53, MetaLR 0.95, Pathogenic, Rare genetic deafness; Nonsyndromic genetic hearing loss; not provided
- A40T (p.Ala40Thr), rs764693395, ClinGen CA6904316, ClinVar RCV002690467, ExAC rs764693395, REVEL 0.71, MetaLR 0.95, Likely pathogenic, not provided
- A40A (p.Ala40Ala), rs561870637, gnomAD 13-20189462-T-G, CADD 0.35
- K41N (p.Lys41Asn), cosmic curated COSV10124, MetaLR 0.78, MetaSVM 0.33
- K41R (p.Lys41Arg), rs866127155, ClinGen CA246460871, cosmic curated COSV10822, ClinVar RCV001981346, REVEL 0.64, MetaLR 0.87, Uncertain significance, not provided
- K41T (p.Lys41Thr), gnomAD 13-20189460-T-G, REVEL 0.73, MetaLR 0.88
- K41E (p.Lys41Glu), gnomAD 13-20189461-T-C, REVEL 0.44, MetaLR 0.52
- E42* (p.Glu42Ter), cosmic curated COSV67010
- E42D (p.Glu42Asp), rs535635403, ClinGen CA6904314, ClinVar RCV001810543, ClinVar RCV002541486, REVEL 0.34, MetaLR 0.81, Conflicting interpretations, not provided; not specified; Autosomal recessive nonsyndromic hearing loss 1A
- E42E (p.Glu42Glu), rs535635403, gnomAD 13-20189456-C-T, CADD 5.62
- V43A (p.Val43Ala), rs776267945, ClinGen CA6904313, ClinVar RCV003127019, ClinVar RCV005011230, REVEL 0.94, MetaLR 0.97, Pathogenic/Likely pathogenic, not provided; Knuckle pads, deafness AND leukonychia syndrome; Autosomal dominan
- V43G (p.Val43Gly), ExAC rs776267945, TOPMed rs776267945, gnomAD rs776267945, MetaLR 0.99, MetaSVM 1.02, Likely pathogenic, Autosomal recessive nonsyndromic hearing loss 1A
- W44* (p.Trp44Ter), rs104894407, ClinGen CA172211, ClinVar RCV000146007, ClinVar RCV000593364, AlphaMissense 1.00, MetaLR 0.98, Pathogenic, in DFNA3A
- W44C (p.Trp44Cys), rs104894407, ClinGen CA257679, ClinVar RCV000018545, UniProt VAR 008709, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, Autosomal recessive nonsyndromic hearing loss 1A
- W44S (p.Trp44Ser), rs104894413, ClinGen CA257682, ClinVar RCV000018559, ClinVar RCV006362024, AlphaMissense 0.99, MetaLR 0.98, Likely pathogenic, Inborn genetic diseases
- G45E (p.Gly45Glu), rs72561723, ClinGen CA127033, cosmic curated COSV10749, ClinVar RCV000018561, REVEL 0.96, MetaLR 0.97, Pathogenic, Mutilating keratoderma; Ichthyosis, hystrix-like, with hearing loss; Autosomal d
- G45R (p.Gly45Arg), rs1326514987, ClinGen CA387461860, NCI-TCGA Cosmic COSV1012, cosmic curated COSV10124, REVEL 0.90, MetaLR 0.98, Conflicting interpretations, Inborn genetic diseases; not provided; Autosomal recessive nonsyndromic hearing
- G45G (p.Gly45Gly), rs777528049, gnomAD 13-20189447-T-A, CADD 7.02
- G45* (p.Gly45Ter), gnomAD 13-20189449-C-A, CADD 38.00
- D46E (p.Asp46Glu), UniProt VAR 060798, Pathogenic, in DFNA3A
- D46H (p.Asp46His), rs1064797088, ClinGen CA387461847, ClinVar RCV001806947, Ensembl rs1064797088, AlphaMissense 0.97, MetaLR 0.99, Likely pathogenic, not provided
- D46N (p.Asp46Asn), rs1064797088, ClinGen CA16621541, ClinVar RCV000487475, ClinVar RCV003558394, AlphaMissense 0.97, MetaLR 0.99, Pathogenic/Likely pathogenic, not provided; Autosomal recessive nonsyndromic hearing loss 1A
- E47* (p.Glu47Ter), rs104894398, ClinGen CA172213, ClinVar RCV000018529, ClinVar RCV000080366, CADD 38.00, Pathogenic
- E47K (p.Glu47Lys), rs104894398, ClinGen CA387461835, ClinVar RCV002474290, ExAC rs104894398, REVEL 0.97, MetaLR 0.99, Conflicting interpretations, not provided
- E47E (p.Glu47Glu), rs370164829, gnomAD 13-20189441-C-T, CADD 7.77
- Q48H (p.Gln48His), gnomAD 13-20189438-C-G, REVEL 0.72, MetaLR 0.97
- A49V (p.Ala49Val), rs1057517976, ClinGen CA16042821, ClinVar RCV000412967, ClinVar RCV000666314, REVEL 0.48, MetaLR 0.89, Conflicting interpretations, not specified; not provided
- A49A (p.Ala49Ala), rs1431278544, gnomAD 13-20189435-G-A, CADD 0.23
- D50N (p.Asp50Asn), rs28931594, ClinGen CA127027, ClinVar RCV000018546, ClinVar RCV000018547, AlphaMissense 0.62, MetaLR 0.98, Pathogenic, Ichthyosis and erythrokeratoderma; Autosomal dominant keratitis-ichthyosis-heari
- D50Y (p.Asp50Tyr), rs28931594, ClinGen CA127031, ClinVar RCV000018556, UniProt VAR 015935, AlphaMissense 0.62, MetaLR 0.98, Likely pathogenic, Autosomal recessive nonsyndromic hearing loss 1A
- F51L (p.Phe51Leu), gnomAD 13-20189428-CA-C, CADD 7.25
- F51C (p.Phe51Cys), rs766340495, gnomAD 13-20189428-CAA-C, CADD 25.20
- V52L (p.Val52Leu), rs1555341987, ClinGen CA6904310, ClinVar RCV000670560, gnomAD rs1555341987, REVEL 0.55, MetaLR 0.91, Uncertain significance, Autosomal recessive nonsyndromic hearing loss 1A
- C53F (p.Cys53Phe), rs587783645, ClinGen CA387461760, ClinVar RCV000785599, Ensembl rs587783645, AlphaMissense 1.00, MetaLR 0.99, Likely pathogenic, Autosomal recessive nonsyndromic hearing loss 1A
- C53R (p.Cys53Arg), rs1555341986, ClinGen CA387461766, ClinVar RCV000667670, ClinVar RCV005418285, REVEL 0.97, AlphaMissense 1.00, Uncertain significance, not specified
- C53S (p.Cys53Ser), rs1555341986, ClinGen CA387461767, ClinVar RCV002051744, Ensembl rs1555341986, AlphaMissense 1.00, MetaLR 0.99, Pathogenic, Autosomal recessive nonsyndromic hearing loss 1A
- C53Y (p.Cys53Tyr), rs587783645, ClinGen CA172215, cosmic curated COSV10822, ClinVar RCV000146009, REVEL 0.97, AlphaMissense 1.00, Pathogenic, Hearing impairment
- C53W (p.Cys53Trp), gnomAD 13-20189423-G-C, REVEL 0.95, MetaLR 0.99
- C53C (p.Cys53Cys), rs888444898, gnomAD 13-20189423-G-A, CADD 8.34
- N54K (p.Asn54Lys), rs104894412, ClinGen CA127032, ClinVar RCV000018558, UniProt VAR 032750, AlphaMissense 1.00, MetaLR 0.98, Pathogenic, Knuckle pads, deafness AND leukonychia syndrome
- N54S (p.Asn54Ser), rs2137308512, ClinGen CA387461749, ClinVar RCV001824481, ClinVar RCV005006082, AlphaMissense 0.64, MetaLR 0.98, Conflicting interpretations, Ichthyosis, hystrix-like, with hearing loss; Autosomal dominant nonsyndromic hea
- N54N (p.Asn54Asn), rs104894412, gnomAD 13-20189420-G-A, AlphaMissense 1.00, MetaLR 0.98
- T55I (p.Thr55Ile), NCI-TCGA Cosmic COSV1012, cosmic curated COSV10124, Variant assessed as somatic; moderate impact.
- T55N (p.Thr55Asn), rs1064797089, ClinGen CA16621540, ClinVar RCV000487478, Ensembl rs1064797089, AlphaMissense 0.85, MetaLR 0.99, not provided, Autosomal dominant nonsyndromic hearing loss 3A
- T55P (p.Thr55Pro), Ensembl rs1593351580
- T55T (p.Thr55Thr), gnomAD 13-20189417-G-A, CADD 0.25
- L56R (p.Leu56Arg), rs80338942, gnomAD 13-20189414-CA-C, CADD 23.40
- Q57* (p.Gln57Ter), rs111033297, ClinGen CA261637, ClinVar RCV000211761, ClinVar RCV000505512, CADD 38.00, Pathogenic
- P58A (p.Pro58Ala), rs1064797090, ClinGen CA16621539, ClinVar RCV000487476, Ensembl rs1064797090, AlphaMissense 0.91, MetaLR 0.98, not provided, Autosomal dominant nonsyndromic hearing loss 3A
- P58Q (p.Pro58Gln), TOPMed rs894732036
- P58S (p.Pro58Ser), rs1064797090, ClinGen CA387461710, ClinVar RCV000623392, Ensembl rs1064797090, AlphaMissense 0.91, MetaLR 0.98, Likely pathogenic, Autosomal dominant nonsyndromic hearing loss 3A
- P58P (p.Pro58Pro), rs778922005, gnomAD 13-20189408-T-C, CADD 0.30
- G59A (p.Gly59Ala), rs104894404, ClinGen CA127026, ClinVar RCV000018540, UniProt VAR 009965, REVEL 0.97, AlphaMissense 0.96, Likely pathogenic, Autosomal recessive nonsyndromic hearing loss 1A
- G59D (p.Gly59Asp), rs104894404, ClinGen CA273153, ClinVar RCV000150733, Ensembl rs104894404, AlphaMissense 0.96, MetaLR 0.99, Likely pathogenic, Rare genetic deafness
- G59R (p.Gly59Arg), rs104894410, ClinGen CA387461703, ClinVar RCV000588875, Ensembl rs104894410, AlphaMissense 0.97, MetaLR 0.99, Pathogenic/Likely pathogenic, Autosomal recessive nonsyndromic hearing loss 1A; Palmoplantar keratoderma-deafn
- G59S (p.Gly59Ser), rs104894410, ClinGen CA127035, ClinVar RCV000018562, ClinVar RCV001851915, AlphaMissense 0.97, MetaLR 0.99, Conflicting interpretations, not provided; Autosomal recessive nonsyndromic hearing loss 1A
- G59V (p.Gly59Val), rs104894404, ClinGen CA387461699, ClinVar RCV002013660, Ensembl rs104894404, AlphaMissense 0.96, MetaLR 0.99, Pathogenic/Likely pathogenic, not provided
- G59G (p.Gly59Gly), rs375122728, gnomAD 13-20189405-G-A, CADD 2.16
- C60F (p.Cys60Phe), Ensembl rs1179195570
- C60G (p.Cys60Gly), rs938857026, ClinGen CA387461695, ClinVar RCV003734641, AlphaMissense 1.00, MetaLR 0.99, Pathogenic, not provided
- C60R (p.Cys60Arg), TOPMed rs938857026, gnomAD rs938857026, REVEL 0.97, AlphaMissense 1.00, Uncertain significance, Autosomal recessive nonsyndromic hearing loss 1A
- C60Y (p.Cys60Tyr), cosmic curated COSV67010, REVEL 0.98, MetaLR 0.99
- K61K (p.Lys61Lys), rs750618125, gnomAD 13-20189399-C-T, CADD 1.29
- N62K (p.Asn62Lys), ExAC rs397516869, TOPMed rs397516869, gnomAD rs397516869, REVEL 0.79, MetaLR 0.98, Likely benign
- N62S (p.Asn62Ser), gnomAD rs1279221857, REVEL 0.51, MetaLR 0.93
- N62N (p.Asn62Asn), rs397516869, gnomAD 13-20189396-G-A, CADD 0.08
- V63A (p.Val63Ala), rs727504309, ClinGen CA180700, ClinVar RCV000154364, ClinVar RCV000711348, REVEL 0.95, MetaLR 0.98, Conflicting interpretations, Mutilating keratoderma; Ichthyosis, hystrix-like, with hearing loss; Autosomal d
- V63L (p.Val63Leu), rs370696868, ClinGen CA6904306, ClinVar RCV000668102, ClinVar RCV001857901, REVEL 0.93, MetaLR 0.98, Likely pathogenic, not provided
- V63M (p.Val63Met), rs370696868, ClinGen CA222244, cosmic curated COSV67010, ClinVar RCV000080367, REVEL 0.88, MetaLR 0.98, Likely pathogenic, not provided; Autosomal recessive nonsyndromic hearing loss 1A
- C64F (p.Cys64Phe), cosmic curated COSV10749, MetaLR 0.99, MetaSVM 0.97
- C64Y (p.Cys64Tyr), rs2500252361, ClinGen CA387461656, ClinVar RCV003331811, REVEL 0.98, MetaLR 0.99, Uncertain significance, not specified
- Y65* (p.Tyr65Ter), rs763572195, ClinGen CA387461648, ClinVar RCV000778388, ClinVar RCV001231552, CADD 33.00, Pathogenic
- Y65C (p.Tyr65Cys), rs111033203, ClinGen CA261639, ClinVar RCV000037819, ClinVar RCV001731333, REVEL 0.99, MetaLR 0.99, Conflicting interpretations, Mutilating keratoderma; Autosomal recessive nonsyndromic hearing loss 1A; Autoso
Public GJB2 analysis runs
- GJB2 analysis run — GJB2 (681 variants) — completed 2026-08-18