CLDN14 (Claudin-14) variants and mutations
CLDN14 (also known as Claudin-14) is a human protein-coding gene encoding a claudin-14 protein. Its annotated function is plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. It is annotated at the cell junction, tight junction. This analysis covers 634 CLDN14 variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes hearing loss, autosomal recessive, deafness, and nephrolithiasis. Example CLDN14 variants include A2V, A2S, and A2T.
Variant analysis overview
- Gene: CLDN14
- Protein: Claudin-14
- UniProt accession: O95500
- Organism: Homo sapiens
- Variants analyzed: 634
- Variant scope: all variants
- Completed: 2026-08-28
Variant and mutation evidence
- Variant composition: 336 unspecified-consequence records; 137 synonymous variants; 128 missense variants; 8 stop-gained variants; 16 frameshift variants; 9 in-frame deletions
- Prediction scores: 527 variants have prediction scores (83% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hearing loss, autosomal recessive, deafness, nephrolithiasis, gout, vein of Galen aneurysm, Hearing impairment, ureterolithiasis, urolithiasis, bladder calculus, nonsyndromic genetic hearing loss, Non-syndromic genetic deafness, hearing loss disorder.
Protein structure and variant hotspots
- Protein features: 4 transmembrane segments.
- Structural context: 234 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, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable CLDN14 variants
Examples include A2V, A2S, A2T, S3G, S3S, T4A, T4K, T4M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2V (p.Ala2Val), gnomAD 21-36461691-G-A, REVEL 0.51, CADD 19.50
- A2S (p.Ala2Ser), gnomAD 21-36461692-C-A, REVEL 0.47, CADD 24.10
- A2T (p.Ala2Thr), gnomAD 21-36461692-C-T, REVEL 0.60, CADD 23.30
- S3G (p.Ser3Gly), TOPMed rs1245862412
- S3S (p.Ser3Ser), gnomAD 21-36461687-G-A, CADD 8.22
- T4A (p.Thr4Ala), ESP rs374578221, ExAC rs374578221, TOPMed rs374578221, gnomAD rs374578221, REVEL 0.08, CADD 13.80, Uncertain significance, not provided
- T4K (p.Thr4Lys), cosmic curated COSV59774
- T4M (p.Thr4Met), rs113831133, ClinGen CA133522, cosmic curated COSV10740, ClinVar RCV000037059, REVEL 0.17, CADD 9.58, Benign/Likely benign, not specified; not provided; Autosomal recessive nonsyndromic hearing loss 29
- T4T (p.Thr4Thr), rs764358289, gnomAD 21-36461684-C-T, CADD 2.95
- A5G (p.Ala5Gly), cosmic curated COSV59776
- A5A (p.Ala5Ala), rs387907416, gnomAD 21-36461681-G-A, CADD 5.20
- A5V (p.Ala5Val), gnomAD 21-36461682-G-A, REVEL 0.74, CADD 24.90
- A5T (p.Ala5Thr), gnomAD 21-36461683-C-T, REVEL 0.78, CADD 23.50
- A5S (p.Ala5Ser), gnomAD 21-36461683-C-A, REVEL 0.65, CADD 22.90
- V6G (p.Val6Gly), Ensembl rs1601588858
- V6L (p.Val6Leu), NCI-TCGA TCGA novel, REVEL 0.29, CADD 13.00, Variant assessed as somatic; moderate impact.
- V6M (p.Val6Met), 1000Genomes rs202117396, ExAC rs202117396, TOPMed rs202117396, gnomAD rs202117396, REVEL 0.37, CADD 23.60
- V6V (p.Val6Val), rs387907417, gnomAD 21-36461678-C-T, CADD 6.55
- Q7* (p.Gln7Ter), TOPMed rs1023845285, gnomAD rs1023845285, CADD 37.00
- Q7R (p.Gln7Arg), NCI-TCGA TCGA novel, 1000Genomes rs2086578304, TOPMed rs2086578304, REVEL 0.93, CADD 24.80, Variant assessed as somatic; moderate impact.
- Q7H (p.Gln7His), gnomAD 21-36461675-C-A, REVEL 0.86, CADD 22.90
- Q7K (p.Gln7Lys), gnomAD 21-36461677-G-T, REVEL 0.80, CADD 24.10
- L8F (p.Leu8Phe), TOPMed rs1399944739, REVEL 0.77, CADD 24.40
- L8H (p.Leu8His), gnomAD 21-36461673-A-T, REVEL 0.97, CADD 25.70
- L9L (p.Leu9Leu), rs1348894244, gnomAD 21-36461669-C-T, CADD 5.85
- G10C (p.Gly10Cys), ExAC rs772295911, TOPMed rs772295911, gnomAD rs772295911, REVEL 0.82, CADD 23.90
- G10R (p.Gly10Arg), ExAC rs772295911, TOPMed rs772295911, gnomAD rs772295911, REVEL 0.88, CADD 23.70
- G10G (p.Gly10Gly), gnomAD 21-36461666-G-A, CADD 6.84
- G10A (p.Gly10Ala), gnomAD 21-36461667-C-G, REVEL 0.81, CADD 23.90
- G10D (p.Gly10Asp), gnomAD 21-36461667-C-T, REVEL 0.87, CADD 24.30
- G10V (p.Gly10Val), gnomAD 21-36461667-C-A, REVEL 0.83, CADD 24.20
- F11F (p.Phe11Phe), rs1217685959, gnomAD 21-36461663-G-A, CADD 8.58
- F11Y (p.Phe11Tyr), gnomAD 21-36461664-A-T, REVEL 0.68, CADD 22.60
- F11V (p.Phe11Val), gnomAD 21-36461665-A-C, REVEL 0.83, CADD 25.70
- L12Q (p.Leu12Gln), gnomAD 21-36461661-A-T, REVEL 0.59, CADD 23.90
- L12L (p.Leu12Leu), gnomAD 21-36461662-G-A, CADD 5.57
- L13L (p.Leu13Leu), gnomAD 21-36461657-G-T, CADD 5.80
- L13F (p.Leu13Phe), gnomAD 21-36461659-G-A, REVEL 0.67, CADD 23.40
- L13I (p.Leu13Ile), gnomAD 21-36461659-G-T, REVEL 0.56, CADD 23.30
- S14I (p.Ser14Ile), NCI-TCGA Cosmic COSV5977, cosmic curated COSV59771, REVEL 0.61, CADD 24.60, Variant assessed as somatic; moderate impact.
- L16P (p.Leu16Pro), gnomAD 21-36461649-A-G, REVEL 0.85, CADD 27.70
- L16M (p.Leu16Met), gnomAD 21-36461650-G-T, REVEL 0.52, CADD 23.20
- G17A (p.Gly17Ala), gnomAD rs1430693827, REVEL 0.92, CADD 24.90
- G17S (p.Gly17Ser), rs1270823192, ClinGen CA409885092, ClinVar RCV001375234, TOPMed rs1270823192, REVEL 0.95, CADD 26.10, Uncertain significance, Alport syndrome
- G17G (p.Gly17Gly), gnomAD 21-36461645-G-T, CADD 9.18
- G17V (p.Gly17Val), gnomAD 21-36461646-C-A, REVEL 0.96, CADD 25.20
- G17D (p.Gly17Asp), gnomAD 21-36461646-C-T, REVEL 0.96, CADD 25.30
- M18T (p.Met18Thr), gnomAD rs1435667810, REVEL 0.41, CADD 23.20
- M18V (p.Met18Val), 1000Genomes rs369883669, ExAC rs369883669, TOPMed rs369883669, gnomAD rs369883669, REVEL 0.23, CADD 18.20
- M18I (p.Met18Ile), gnomAD 21-36461642-C-A, REVEL 0.26, CADD 22.40
- V19E (p.Val19Glu), gnomAD rs1375686770
- V19L (p.Val19Leu), ExAC rs769320772
- V19V (p.Val19Val), gnomAD 21-36461639-C-T, CADD 7.71
- V19M (p.Val19Met), gnomAD 21-36461641-C-T, REVEL 0.43, CADD 22.90
- G20A (p.Gly20Ala), Ensembl rs982935102, REVEL 0.64, CADD 24.80
- G20G (p.Gly20Gly), rs387907415, gnomAD 21-36461636-G-A, CADD 9.51
- G20V (p.Gly20Val), gnomAD 21-36461637-C-A, REVEL 0.81, CADD 25.10
- G20D (p.Gly20Asp), gnomAD 21-36461637-C-T, REVEL 0.89, CADD 25.30
- G20R (p.Gly20Arg), gnomAD 21-36461638-C-G, REVEL 0.91, CADD 25.70
- G20C (p.Gly20Cys), gnomAD 21-36461638-C-A, REVEL 0.77, CADD 26.20
- T21M (p.Thr21Met), rs532176130, NCI-TCGA Cosmic COSV1005, cosmic curated COSV10057, 1000Genomes rs532176130, REVEL 0.74, CADD 25.50, Variant assessed as somatic; moderate impact.
- T21T (p.Thr21Thr), gnomAD 21-36461633-C-A, CADD 2.05
- L22del (p.Leu22del), rs762948927, gnomAD 21-36461629-TCAA-, CADD 17.90
- L22F (p.Leu22Phe), gnomAD 21-36461630-C-A, REVEL 0.57, CADD 16.30
- L22S (p.Leu22Ser), gnomAD 21-36461631-A-G, REVEL 0.60, CADD 24.00
- L22L (p.Leu22Leu), rs1167955774, gnomAD 21-36461632-A-G, CADD 8.98
- I23L (p.Ile23Leu), ExAC rs780834768
- I23T (p.Ile23Thr), ExAC rs768411939, gnomAD rs768411939, REVEL 0.31, CADD 20.70
- I23I (p.Ile23Ile), rs2086577130, gnomAD 21-36461627-G-A, CADD 10.20
- T24P (p.Thr24Pro), Ensembl rs1601588764
- T24T (p.Thr24Thr), rs549639383, gnomAD 21-36461624-G-A, CADD 8.48
- T24N (p.Thr24Asn), gnomAD 21-36461625-G-T, REVEL 0.58, CADD 24.90
- T24A (p.Thr24Ala), gnomAD 21-36461626-T-C, REVEL 0.23, CADD 16.00
- T25I (p.Thr25Ile), ExAC rs779937857, gnomAD rs779937857, REVEL 0.78, CADD 26.50
- T25N (p.Thr25Asn), ExAC rs779937857, gnomAD rs779937857
- T25P (p.Thr25Pro), Ensembl rs1601588758
- T25T (p.Thr25Thr), gnomAD 21-36461621-G-T, CADD 6.47
- I26N (p.Ile26Asn), rs2517047770, ClinGen CA409884810, ClinVar RCV003129506, Uncertain significance, not provided
- I26I (p.Ile26Ile), gnomAD 21-36461618-G-T, CADD 5.36
- I26F (p.Ile26Phe), gnomAD 21-36461620-T-A, REVEL 0.48, CADD 14.80
- L27L (p.Leu27Leu), gnomAD 21-36461615-C-A, CADD 7.08
- L27M (p.Leu27Met), gnomAD 21-36461617-G-T, REVEL 0.64, CADD 23.90
- P28L (p.Pro28Leu), rs727504989, ClinGen CA184779, cosmic curated COSV59777, ClinVar RCV000156406, REVEL 0.82, CADD 26.40, Conflicting interpretations, not specified; not provided
- P28S (p.Pro28Ser), cosmic curated COSV59776, ExAC rs758081638, gnomAD rs758081638, REVEL 0.79, CADD 25.80
- P28P (p.Pro28Pro), rs778927942, gnomAD 21-36461612-C-T, CADD 3.01
- P28Q (p.Pro28Gln), gnomAD 21-36461613-G-T, REVEL 0.84, CADD 25.80
- P28T (p.Pro28Thr), gnomAD 21-36461614-G-T, REVEL 0.86, CADD 25.40
- H29Q (p.His29Gln), gnomAD rs1309453126, REVEL 0.59, CADD 23.40
- W30* (p.Trp30Ter), rs1273842424, ClinGen CA409884708, ClinVar RCV001375278, ClinVar RCV002550952, CADD 37.00, Pathogenic
- W30C (p.Trp30Cys), cosmic curated COSV10818
- W30R (p.Trp30Arg), cosmic curated COSV59778
- R31Q (p.Arg31Gln), rs1041031415, ClinGen CA320314382, ClinVar RCV002679508, TOPMed rs1041031415, REVEL 0.38, CADD 17.30, Uncertain significance, Inborn genetic diseases
- R31W (p.Arg31Trp), rs757426764, ClinGen CA10019345, ClinVar RCV003152079, ClinVar RCV006342921, REVEL 0.40, CADD 21.70, Uncertain significance, not provided; Inborn genetic diseases
- R31R (p.Arg31Arg), rs1295583562, gnomAD 21-36461603-C-T, CADD 1.52
- R31G (p.Arg31Gly), gnomAD 21-36461605-G-C, REVEL 0.59, CADD 24.00
- R32K (p.Arg32Lys), gnomAD rs2086576470, REVEL 0.45, CADD 17.60
- R32S (p.Arg32Ser), rs886057050, ClinGen CA10650456, ClinVar RCV000343853, gnomAD rs886057050, REVEL 0.58, CADD 0.99, Uncertain significance, Autosomal recessive nonsyndromic hearing loss 29
- R32M (p.Arg32Met), gnomAD 21-36461601-C-A, REVEL 0.44, CADD 22.60
- T33I (p.Thr33Ile), Ensembl rs1183327479
- T33T (p.Thr33Thr), rs899830471, gnomAD 21-36461597-T-C, CADD 0.27
- A34E (p.Ala34Glu), ExAC rs754032374, TOPMed rs754032374, gnomAD rs754032374, REVEL 0.76, CADD 24.20, Uncertain significance
- A34V (p.Ala34Val), rs754032374, ClinGen CA409884581, ClinVar RCV002771818, ExAC rs754032374, REVEL 0.72, CADD 24.40, Uncertain significance, Inborn genetic diseases
- A34A (p.Ala34Ala), rs146395322, gnomAD 21-36461594-C-A, CADD 0.29
- H35R (p.His35Arg), Ensembl rs2146412001
- H35H (p.His35His), rs560763542, gnomAD 21-36461591-G-A, CADD 1.78
- H35Q (p.His35Gln), gnomAD 21-36461591-G-T, REVEL 0.61, CADD 20.00
- H35N (p.His35Asn), gnomAD 21-36461593-G-T, REVEL 0.61, CADD 23.50
- V36L (p.Val36Leu), ESP rs142205038, ExAC rs142205038, TOPMed rs142205038, gnomAD rs142205038, REVEL 0.65, CADD 23.30, Uncertain significance
- V36M (p.Val36Met), rs142205038, ClinGen CA10019340, cosmic curated COSV59775, ClinVar RCV002026765, REVEL 0.64, CADD 23.70, Uncertain significance, not provided
- G37S (p.Gly37Ser), ExAC rs759850341, gnomAD rs759850341, REVEL 0.77, CADD 25.30
- G37G (p.Gly37Gly), gnomAD 21-36461585-G-A, CADD 9.60
- G37V (p.Gly37Val), gnomAD 21-36461586-C-A, REVEL 0.77, CADD 24.60
- G37D (p.Gly37Asp), gnomAD 21-36461586-C-T, REVEL 0.76, CADD 24.60
- T38N (p.Thr38Asn), TOPMed rs1401609630, gnomAD rs1401609630, REVEL 0.29, CADD 22.60, Uncertain significance, Inborn genetic diseases
- T38I (p.Thr38Ile), gnomAD 21-36461583-G-A, REVEL 0.55, CADD 24.10
- T38P (p.Thr38Pro), gnomAD 21-36461583-GT-G, CADD 26.60
- N39del (p.Asn39del), rs752639706, gnomAD 21-36461577-ATGT-, CADD 18.90
- N39N (p.Asn39Asn), rs2086576026, gnomAD 21-36461579-G-A, CADD 7.54
- N39D (p.Asn39Asp), gnomAD 21-36461581-T-C, REVEL 0.71, CADD 26.20
- L41I (p.Leu41Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L41F (p.Leu41Phe), gnomAD 21-36461575-G-A, REVEL 0.47, CADD 22.90
- T42A (p.Thr42Ala), cosmic curated COSV59771
- T42M (p.Thr42Met), ExAC rs533194857, TOPMed rs533194857, gnomAD rs533194857, REVEL 0.82, CADD 26.70
- T42T (p.Thr42Thr), rs140177046, gnomAD 21-36461570-C-T, CADD 7.22
- T42K (p.Thr42Lys), gnomAD 21-36461571-G-T, REVEL 0.89, CADD 26.70
- A43A (p.Ala43Ala), rs150731625, gnomAD 21-36461567-G-A, CADD 11.40
- V44M (p.Val44Met), rs141139613, ClinGen CA10019334, ClinVar RCV002732081, ClinVar RCV005242322, REVEL 0.52, CADD 24.90, Uncertain significance, Inborn genetic diseases; not provided
- S45F (p.Ser45Phe), TOPMed rs1044825412, gnomAD rs1044825412, REVEL 0.41, CADD 22.80, Uncertain significance, Nonsyndromic genetic hearing loss
- Y46F (p.Tyr46Phe), cosmic curated COSV10818
- L47L (p.Leu47Leu), gnomAD 21-36461555-C-T, CADD 8.71
- L47M (p.Leu47Met), gnomAD 21-36461557-G-T, REVEL 0.25, CADD 15.30
- K48* (p.Lys48Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K48R (p.Lys48Arg), gnomAD rs947811327, REVEL 0.63, CADD 23.80
- G49E (p.Gly49Glu), TOPMed rs1347733089, gnomAD rs1347733089, REVEL 0.85, CADD 25.40
- G49R (p.Gly49Arg), NCI-TCGA Cosmic COSV5977, cosmic curated COSV59775, Variant assessed as somatic; moderate impact.
- L50L (p.Leu50Leu), gnomAD 21-36461546-G-T, CADD 5.41
- W51C (p.Trp51Cys), gnomAD 21-36461543-C-A, REVEL 0.93, CADD 28.30
- W51* (p.Trp51Ter), gnomAD 21-36461544-C-T, CADD 39.00
- M52I (p.Met52Ile), rs1481757019, ClinGen CA409883789, ClinVar RCV002265361, ClinVar RCV005542740, REVEL 0.86, CADD 25.70, Uncertain significance, not provided; Inborn genetic diseases
- E53A (p.Glu53Ala), Ensembl rs1601588619
- E53E (p.Glu53Glu), rs768019537, gnomAD 21-36461537-C-T, CADD 8.43
- E53K (p.Glu53Lys), gnomAD 21-36461539-C-T, REVEL 0.77, CADD 26.70
- C54C (p.Cys54Cys), rs746698259, gnomAD 21-36461534-A-G, CADD 7.18
- C54W (p.Cys54Trp), gnomAD 21-36461534-A-C, REVEL 0.82, CADD 23.00
- C54S (p.Cys54Ser), gnomAD 21-36461535-C-G, REVEL 0.96, CADD 25.70
- C54Y (p.Cys54Tyr), gnomAD 21-36461535-C-T, REVEL 0.96, CADD 26.20
- V55A (p.Val55Ala), ExAC rs752960573, gnomAD rs752960573, REVEL 0.68, CADD 22.50
- W56* (p.Trp56Ter), rs371100799, ClinGen CA199223, cosmic curated COSV59776, ClinVar RCV000169748, CADD 39.00, Pathogenic
- W56S (p.Trp56Ser), rs765103185, gnomAD 21-36461527-GCC-G, CADD 28.10
- H57Q (p.His57Gln), ExAC rs778842030, TOPMed rs778842030, gnomAD rs778842030, REVEL 0.51, CADD 18.90, Uncertain significance, not provided
- H57Y (p.His57Tyr), rs745601274, ClinGen CA10019330, ClinVar RCV001375125, ExAC rs745601274, REVEL 0.55, CADD 21.60, Uncertain significance, Hearing impairment
- H57H (p.His57His), rs778842030, gnomAD 21-36461525-G-A, CADD 8.40
- S58N (p.Ser58Asn), gnomAD 21-36461523-C-T, REVEL 0.68, CADD 24.50
- S58G (p.Ser58Gly), gnomAD 21-36461524-T-C, REVEL 0.82, CADD 25.60
- T59I (p.Thr59Ile), gnomAD 21-36461520-G-A, REVEL 0.78, CADD 25.50
- T59R (p.Thr59Arg), gnomAD 21-36461520-G-C, REVEL 0.80, CADD 25.50
- G60D (p.Gly60Asp), TOPMed rs1273080082, gnomAD rs1273080082, REVEL 0.95, CADD 26.00
- I61F (p.Ile61Phe), rs757334760, ClinGen CA10019327, ClinVar RCV002642218, ExAC rs757334760, REVEL 0.55, CADD 24.00, Uncertain significance, not provided
- I61M (p.Ile61Met), TOPMed rs2086574716
- p.Ile61 Tyr62del, rs1225780661, gnomAD 21-36461509-GGTAG, CADD 18.90
- I61I (p.Ile61Ile), gnomAD 21-36461513-G-T, CADD 8.97
- I61V (p.Ile61Val), gnomAD 21-36461515-T-C, REVEL 0.23, CADD 17.40
- Y62* (p.Tyr62Ter), cosmic curated COSV59775, gnomAD rs1234859445, CADD 39.00
- Y62C (p.Tyr62Cys), rs148223897, ClinGen CA10019326, ClinVar RCV000219015, ClinVar RCV001594877, REVEL 0.74, CADD 26.80, Conflicting interpretations, not provided; Vein of Galen aneurysmal malformation; not specified
- Q63H (p.Gln63His), TOPMed rs981704813, gnomAD rs981704813, REVEL 0.73, CADD 24.70
- Q63R (p.Gln63Arg), gnomAD 21-36461507-CT-C, CADD 29.50
- Q63Q (p.Gln63Gln), rs981704813, gnomAD 21-36461507-C-T, CADD 8.98
- C64Y (p.Cys64Tyr), rs1568839335, ClinGen CA409883247, ClinVar RCV000735776, Ensembl rs1568839335, REVEL 0.95, CADD 26.10, Likely pathogenic, Autosomal recessive nonsyndromic hearing loss 29
- C64G (p.Cys64Gly), gnomAD 21-36461506-A-C, REVEL 0.96, CADD 27.90
- Q65* (p.Gln65Ter), TOPMed rs1480611097, gnomAD rs1480611097, CADD 40.00
- Q65Q (p.Gln65Gln), rs777960789, gnomAD 21-36461501-C-T, CADD 8.82
- Q65R (p.Gln65Arg), gnomAD 21-36461502-T-C, REVEL 0.60, CADD 25.20
- I66T (p.Ile66Thr), gnomAD rs2086574212, REVEL 0.19, CADD 21.40
- I66V (p.Ile66Val), TOPMed rs1377319591
- I66S (p.Ile66Ser), rs760769965, gnomAD 21-36461500-TC-T, CADD 26.60
- Y67* (p.Tyr67Ter), gnomAD 21-36461495-G-T, CADD 40.00
- Y67Y (p.Tyr67Tyr), rs1397562843, gnomAD 21-36461495-G-A, CADD 8.00
- R68* (p.Arg68Ter), TOPMed rs865872458, gnomAD rs865872458, CADD 42.00
- R68Q (p.Arg68Gln), ExAC rs756095919, TOPMed rs756095919, gnomAD rs756095919, REVEL 0.37, CADD 22.50
- S69F (p.Ser69Phe), cosmic curated COSV59773, Uncertain significance, Inborn genetic diseases
Public CLDN14 analysis runs
- CLDN14 analysis run — CLDN14 (634 variants) — completed 2026-08-28