COL4A4 (Collagen alpha-4(IV) chain) variants and mutations
COL4A4 (also known as Collagen alpha-4(IV) chain) is a human protein-coding gene encoding a collagen alpha-4(IV) chain protein. It combines with the alpha3 and alpha5 chains to form the mature type IV collagen network of glomerular, cochlear, and ocular basement membranes. Pathogenic variants cause autosomal Alport-spectrum disease and can present with isolated persistent hematuria. This analysis covers 2,719 COL4A4 variants and mutations. Of these, 85% have computational variant effect predictions. Disease context includes autosomal recessive Alport syndrome, hematuria, benign familial, 1, and Hematuria. Example COL4A4 variants include W2*, W2C, and S3F.
Variant analysis overview
- Gene: COL4A4
- Protein: Collagen alpha-4(IV) chain
- UniProt accession: P53420
- Organism: Homo sapiens
- Variants analyzed: 2719
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 2,466 unspecified-consequence records; 7 in-frame deletions; 92 synonymous variants; 116 missense variants; 26 frameshift variants; 8 stop-gained variants; 2 in-frame insertions; 1 splice-region variants; 1 substitution
- Prediction scores: 2,316 variants have prediction scores (85% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: autosomal recessive Alport syndrome, hematuria, benign familial, 1, Hematuria, Alport syndrome, Benign familial neonatal seizures, autosomal dominant Alport syndrome, Dupuytren Contracture, Abnormality of the urinary system, hereditary disease, hematuria, benign familial, glomerulonephritis, Skin ulcer.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 post-translational modification sites.
- Structural context: 530 variants have structural context.
- PTM context: 1 variants overlap post-translational modification sites.
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, MaveDB, LitVar.
Notable COL4A4 variants
Examples include W2*, W2C, S3F, S3T, L4A, L4P, H5N, H5R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- W2* (p.Trp2Ter), rs1382380215, ClinGen CA350842881, ClinVar RCV002037697, NCI-TCGA TCGA novel, AlphaMissense 0.14, MetaLR 0.35, Pathogenic
- W2C (p.Trp2Cys), gnomAD rs1382380215, REVEL 0.23, AlphaMissense 0.14, Pathogenic
- S3F (p.Ser3Phe), rs201403066, ClinGen CA2145873, ClinVar RCV000928067, ClinVar RCV001274064, REVEL 0.19, CADD 1.01, Conflicting interpretations, not provided; Autosomal recessive Alport syndrome; Hematuria, benign familial, 1
- S3T (p.Ser3Thr), ExAC rs755957159, TOPMed rs755957159, gnomAD rs755957159, REVEL 0.15, CADD 0.02
- L4A (p.Leu4Ala), rs2477329625, ClinGen CA2580616722, ClinVar RCV002468839, ClinVar RCV005429082, Likely pathogenic
- L4P (p.Leu4Pro), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- H5N (p.His5Asn), gnomAD rs1212871805, REVEL 0.16, CADD 2.85
- H5R (p.His5Arg), gnomAD rs1441153596, MetaLR 0.35, MetaSVM -0.75
- I6L (p.Ile6Leu), ExAC rs763492958, TOPMed rs763492958, gnomAD rs763492958, REVEL 0.23, CADD 0.18, Uncertain significance
- I6T (p.Ile6Thr), rs16823264, ClinGen CA2145868, ClinVar RCV000248898, ClinVar RCV000286526, REVEL 0.17, CADD 0.89, Benign/Likely benign, not specified; not provided; Alport syndrome
- I6V (p.Ile6Val), rs763492958, ClinGen CA2145869, ClinVar RCV003155732, ExAC rs763492958, REVEL 0.12, CADD 0.05, Uncertain significance, not specified
- V7E (p.Val7Glu), gnomAD rs1310995837, REVEL 0.20, CADD 1.64
- L8P (p.Leu8Pro), gnomAD 2-227010476-A-G, CADD 3.43, SIFT 0.00
- M9I (p.Met9Ile), NCI-TCGA Cosmic COSV6163, Variant assessed as somatic; moderate impact.
- M9K (p.Met9Lys), rs1440047357, ClinGen CA350842844, ClinVar RCV001946526, ClinVar RCV006257009, REVEL 0.27, AlphaMissense 0.12, Uncertain significance, Benign familial hematuria; Autosomal recessive Alport syndrome; not provided
- M9T (p.Met9Thr), rs1440047357, ClinGen CA350842843, ClinVar RCV002623308, TOPMed rs1440047357, AlphaMissense 0.12, MetaLR 0.41, Uncertain significance, not provided
- M9V (p.Met9Val), ExAC rs775856971, TOPMed rs775856971, gnomAD rs775856971, REVEL 0.19, CADD 0.01
- R10K (p.Arg10Lys), gnomAD rs1284205772, REVEL 0.12, CADD 1.15
- C11F (p.Cys11Phe), ExAC rs770345405, gnomAD rs770345405
- C11Y (p.Cys11Tyr), ExAC rs770345405, gnomAD rs770345405, MetaLR 0.44, MetaSVM -0.64, Uncertain significance, Alport syndrome
- R14G (p.Arg14Gly), ExAC rs777010630, TOPMed rs777010630, gnomAD rs777010630, REVEL 0.16, CADD 10.20
- R14I (p.Arg14Ile), rs771093210, NCI-TCGA Cosmic COSV1003, ExAC rs771093210, AlphaMissense 0.11, MetaLR 0.48, Uncertain significance, not provided
- R14Q (p.Arg14Gln), rs750682352, gnomAD 2-227010413-C-T, CADD 1.16, SIFT 0.52
- K17N (p.Lys17Asn), ExAC rs748315118, TOPMed rs748315118, gnomAD rs748315118, MetaLR 0.41, MetaSVM -0.51, Likely benign
- K17R (p.Lys17Arg), rs114969026, ClinGen CA2145860, ClinVar RCV000480643, ClinVar RCV000904082, REVEL 0.15, CADD 14.70, Benign/Likely benign, not specified; Alport syndrome; not provided
- K17* (p.Lys17Ter), rs770419378, gnomAD 2-227010468-T-A, REVEL 0.22, MetaLR 0.56
- S18A (p.Ser18Ala), Ensembl rs2063621553
- S18F (p.Ser18Phe), TOPMed rs1472124369, gnomAD rs1472124369, REVEL 0.18, CADD 4.17
- S18L (p.Ser18Leu), rs757955398, gnomAD 2-227010446-G-A, CADD 2.29, SIFT 0.00
- L19W (p.Leu19Trp), gnomAD rs1237383434, REVEL 0.37, CADD 12.40
- A20V (p.Ala20Val), gnomAD 2-227010386-G-A, CADD 13.80, SIFT 0.08
- T21R (p.Thr21Arg), NCI-TCGA Cosmic COSV1003, REVEL 0.23, CADD 5.65, Variant assessed as somatic; moderate impact.
- T21I (p.Thr21Ile), rs2149743323, gnomAD 2-227010317-G-A, CADD 8.39, SIFT 0.01
- G22D (p.Gly22Asp), NCI-TCGA Cosmic COSV6162, Ensembl rs2125387839, Variant assessed as somatic; moderate impact.
- G22S (p.Gly22Ser), rs779795137, ClinGen CA2145858, ClinVar RCV001771518, ClinVar RCV006256915, REVEL 0.12, CADD 2.33, Uncertain significance, Autosomal recessive Alport syndrome; Benign familial hematuria; not provided
- G22V (p.Gly22Val), gnomAD 2-227010500-C-A, CADD 0.39, SIFT 0.00
- P23H (p.Pro23His), gnomAD rs1284248647, REVEL 0.41, CADD 13.30
- P23S (p.Pro23Ser), ExAC rs756127918, TOPMed rs756127918, gnomAD rs756127918, REVEL 0.10, CADD 5.42
- P23T (p.Pro23Thr), ExAC rs756127918, TOPMed rs756127918, gnomAD rs756127918, REVEL 0.17, CADD 8.66
- P23L (p.Pro23Leu), rs1343679990, gnomAD 2-227010401-G-A, CADD 6.01, SIFT 0.00
- W24* (p.Trp24Ter), rs2125348371, ClinGen CA350842732, ClinVar RCV002037765, Ensembl rs2125348371, CADD 41.00, Pathogenic
- W24L (p.Trp24Leu), TOPMed rs1201925443, gnomAD rs1201925443, REVEL 0.36, CADD 23.40, Pathogenic
- S25A (p.Ser25Ala), rs2125348343, ClinGen CA350842729, ClinVar RCV002267338, Ensembl rs2125348343, AlphaMissense 0.08, MetaLR 0.40, Uncertain significance, not provided
- S25L (p.Ser25Leu), ESP rs370486963, ExAC rs370486963, TOPMed rs370486963, gnomAD rs370486963, REVEL 0.14, CADD 13.80
- S25F (p.Ser25Phe), rs1963408223, gnomAD 2-227010434-G-A, CADD 8.91, SIFT 0.00
- L26F (p.Leu26Phe), Ensembl rs2063421084
- I27T (p.Ile27Thr), Ensembl rs2125348205
- I29M (p.Ile29Met), TOPMed rs2063420541
- I29N (p.Ile29Asn), TOPMed rs2063420678, REVEL 0.47, CADD 23.00
- L30F (p.Leu30Phe), rs758174051, ClinGen CA2145811, NCI-TCGA Cosmic COSV1043, ClinVar RCV001138180, REVEL 0.13, CADD 3.27, Uncertain significance, Alport syndrome; not provided
- L30P (p.Leu30Pro), TOPMed rs2063420255
- L30R (p.Leu30Arg), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- F31S (p.Phe31Ser), ExAC rs754455472, gnomAD rs754455472, REVEL 0.58, CADD 22.70
- S32C (p.Ser32Cys), rs1360606073, ClinGen CA765660207, ClinVar RCV002828804, ClinVar RCV004782964, Pathogenic
- S32F (p.Ser32Phe), ESP rs377568944, ExAC rs377568944, TOPMed rs377568944, gnomAD rs377568944, REVEL 0.55, CADD 23.80
- S32N (p.Ser32Asn), rs2149744390, gnomAD 2-227010404-C-T, CADD 1.82, SIFT 1.00
- V33I (p.Val33Ile), Ensembl rs2063419467, REVEL 0.18, CADD 3.79
- Q34K (p.Gln34Lys), ExAC rs753355705, TOPMed rs753355705, gnomAD rs753355705, REVEL 0.34, CADD 19.50, Uncertain significance, Autosomal recessive Alport syndrome; Hematuria, benign familial, 1
- Y35* (p.Tyr35Ter), rs756672670, ClinGen CA2145805, ClinVar RCV001922706, ExAC rs756672670, CADD 34.00, Pathogenic
- Y35H (p.Tyr35His), rs2063418861, ClinGen CA350842667, ClinVar RCV002279114, TOPMed rs2063418861, REVEL 0.17, CADD 9.14, Uncertain significance, not provided
- V36A (p.Val36Ala), gnomAD rs1311865804, REVEL 0.10, CADD 0.40
- V36I (p.Val36Ile), TOPMed rs1272885382
- Y37C (p.Tyr37Cys), rs750707504, ClinGen CA2145804, ClinVar RCV001774094, ExAC rs750707504, REVEL 0.19, CADD 10.70, Conflicting interpretations, not provided
- S39C (p.Ser39Cys), gnomAD 2-227010374-G-C, CADD 7.59, SIFT 0.08
- S39F (p.Ser39Phe), gnomAD 2-227010374-G-A, CADD 8.11, SIFT 0.68
- G40* (p.Gly40Ter), rs2125292585, ClinGen CA350866605, ClinVar RCV001380123, Ensembl rs2125292585, Pathogenic
- G40E (p.Gly40Glu), ESP rs370128179, ExAC rs370128179, TOPMed rs370128179, gnomAD rs370128179, REVEL 0.32, CADD 19.00, Uncertain significance, Autosomal recessive Alport syndrome; Hematuria, benign familial, 1
- G40V (p.Gly40Val), NCI-TCGA Cosmic COSV6163, MetaLR 0.47, MetaSVM -0.27, Variant assessed as somatic; moderate impact.
- G40D (p.Gly40Asp), gnomAD 2-227010377-C-T, CADD 10.60, SIFT 0.00
- K41N (p.Lys41Asn), rs1162611784, ClinGen CA350866582, ClinVar RCV001882208, gnomAD rs1162611784, REVEL 0.44, CADD 24.90, Uncertain significance, not provided
- K42T (p.Lys42Thr), NCI-TCGA Cosmic COSV6163, MetaLR 0.71, MetaSVM 0.10, Variant assessed as somatic; moderate impact.
- I44T (p.Ile44Thr), TOPMed rs924312880, REVEL 0.14, CADD 5.12
- I44V (p.Ile44Val), Ensembl rs1576813084, MetaLR 0.35, MetaSVM -0.72
- G45C (p.Gly45Cys), rs753016038, ClinGen CA2145779, ClinVar RCV001769123, ClinVar RCV006256914, REVEL 0.40, CADD 21.50, Conflicting interpretations, Autosomal recessive Alport syndrome; Benign familial hematuria; not provided
- G45R (p.Gly45Arg), ExAC rs753016038, TOPMed rs753016038, gnomAD rs753016038, REVEL 0.34, CADD 18.90, Uncertain significance
- G45D (p.Gly45Asp), rs1308858968, gnomAD 2-227010365-C-T, CADD 9.28, SIFT 0.04
- G45V (p.Gly45Val), rs1308858968, gnomAD 2-227010365-C-A, CADD 8.73, SIFT 0.04
- P46S (p.Pro46Ser), NCI-TCGA Cosmic COSV6163, MetaLR 0.59, MetaSVM -0.27, Variant assessed as somatic; moderate impact.
- P46T (p.Pro46Thr), rs374836502, ClinGen CA2145778, ClinVar RCV003011356, ClinVar RCV005019552, REVEL 0.32, CADD 21.50, Conflicting interpretations, not provided; Autosomal recessive Alport syndrome; Hematuria, benign familial, 1
- P46L (p.Pro46Leu), rs1247246118, gnomAD 2-227010380-G-A, CADD 9.84, SIFT 0.00
- P46R (p.Pro46Arg), rs759470234, gnomAD 2-227010392-G-C, CADD 2.56, SIFT 0.02
- P46H (p.Pro46His), rs759470234, gnomAD 2-227010392-G-T, CADD 2.07, SIFT 0.01
- G48A (p.Gly48Ala), NCI-TCGA Cosmic COSV6163, Variant assessed as somatic; moderate impact.
- G48R (p.Gly48Arg), rs2476902793, ClinGen CA350866463, ClinVar RCV003225401, Uncertain significance, not provided
- G49* (p.Gly49Ter), rs2476902451, ClinGen CA350866449, ClinVar RCV004545948, Pathogenic
- G49E (p.Gly49Glu), NCI-TCGA Cosmic COSV6162, TOPMed rs2063104903, gnomAD rs2063104903, REVEL 0.58, CADD 24.20, Variant assessed as somatic; moderate impact.
- G49D (p.Gly49Asp), gnomAD 2-227010341-C-T, CADD 1.43, SIFT 0.00
- R50G (p.Arg50Gly), NCI-TCGA Cosmic COSV6163, Variant assessed as somatic; moderate impact.
- R50I (p.Arg50Ile), NCI-TCGA Cosmic COSV6163, MetaLR 0.71, MetaSVM 0.41, Variant assessed as somatic; moderate impact.
- R50T (p.Arg50Thr), gnomAD rs1261294446, REVEL 0.54, CADD 24.00
- D51H (p.Asp51His), gnomAD rs1489514277, REVEL 0.59, CADD 23.00
- D51Y (p.Asp51Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C52* (p.Cys52Ter), rs2125291854, ClinGen CA350866388, ClinVar RCV001387061, Ensembl rs2125291854, Pathogenic
- C52F (p.Cys52Phe), ExAC rs773187959, TOPMed rs773187959, gnomAD rs773187959, REVEL 0.58, CADD 24.00
- S53C (p.Ser53Cys), ExAC rs771913348, gnomAD rs771913348, REVEL 0.51, CADD 24.00
- V54G (p.Val54Gly), rs537516406, ClinGen CA2145774, ClinVar RCV002873126, 1000Genomes rs537516406, REVEL 0.32, CADD 11.60, Uncertain significance, Inborn genetic diseases
- C55* (p.Cys55Ter), rs768245333, ClinGen CA350866319, ClinVar RCV002243539, ExAC rs768245333, Pathogenic
- C55F (p.Cys55Phe), rs570529667, ClinGen CA2145773, ClinVar RCV001927883, ClinVar RCV006256978, REVEL 0.65, CADD 24.10, Uncertain significance, not provided; Autosomal recessive Alport syndrome; Benign familial hematuria
- C57* (p.Cys57Ter), rs2476899667, ClinGen CA350866285, ClinVar RCV002310331, Likely pathogenic
- C57R (p.Cys57Arg), rs2476899951, ClinGen CA350866295, ClinVar RCV002469716, REVEL 0.65, CADD 24.30, Uncertain significance, not provided
- V58V (p.Val58Val), rs141793628, gnomAD 2-227008237-C-T, CADD 9.14
- E60Q (p.Glu60Gln), TOPMed rs1317174183, gnomAD rs1317174183, REVEL 0.20, CADD 22.70
- K61R (p.Lys61Arg), gnomAD 2-227010344-T-C, CADD 8.69, SIFT 0.00
- S63F (p.Ser63Phe), NCI-TCGA TCGA novel, MetaLR 0.79, MetaSVM 0.78, Variant assessed as somatic; moderate impact.
- R64P (p.Arg64Pro), ESP rs371326070, ExAC rs371326070, TOPMed rs371326070, gnomAD rs371326070, REVEL 0.59, CADD 24.50, Uncertain significance
- R64Q (p.Arg64Gln), rs371326070, ClinGen CA2145769, NCI-TCGA Cosmic COSV6162, NCI-TCGA Cosmic COSV6163, REVEL 0.31, CADD 21.20, Uncertain significance, Autosomal recessive Alport syndrome; Benign familial hematuria; not provided
- R64W (p.Arg64Trp), rs200668675, ClinGen CA2145770, ClinVar RCV000625690, ClinVar RCV005900093, REVEL 0.62, CADD 29.20, Uncertain significance, Autosomal recessive Alport syndrome; Benign familial hematuria
- G65C (p.Gly65Cys), ExAC rs776036994, TOPMed rs776036994, gnomAD rs776036994, Likely pathogenic
- G65D (p.Gly65Asp), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- G65S (p.Gly65Ser), rs776036994, ClinGen CA350863536, ClinVar RCV001281287, ClinVar RCV004538531, REVEL 0.93, CADD 30.00, Likely pathogenic, Autosomal dominant COL4A4-related disorders; Autosomal recessive Alport syndrome
- G65V (p.Gly65Val), ExAC rs771517961, gnomAD rs771517961, MetaLR 0.99, MetaSVM 1.01, Likely pathogenic, Alport syndrome; Autosomal recessive Alport syndrome; Hematuria, benign familial
- P66L (p.Pro66Leu), TOPMed rs1182359031, REVEL 0.30, CADD 9.34
- P66S (p.Pro66Ser), rs758822531, ClinGen CA2145746, ClinVar RCV003073990, ClinVar RCV005028153, REVEL 0.41, CADD 23.00, Conflicting interpretations, not provided; Autosomal recessive Alport syndrome; Hematuria, benign familial, 1
- P67A (p.Pro67Ala), ExAC rs755183371, TOPMed rs755183371, gnomAD rs755183371, REVEL 0.71, CADD 24.70, Uncertain significance, not provided
- P67S (p.Pro67Ser), ExAC rs755183371, TOPMed rs755183371, gnomAD rs755183371, REVEL 0.78, CADD 25.40, Uncertain significance, Autosomal recessive Alport syndrome; Hematuria, benign familial, 1; not provided
- G68* (p.Gly68Ter), NCI-TCGA Cosmic COSV6163, Variant assessed as somatic; high impact.
- G68V (p.Gly68Val), ExAC rs753903329, TOPMed rs753903329, gnomAD rs753903329, REVEL 0.94, CADD 25.40, Likely pathogenic, Autosomal recessive Alport syndrome; Hematuria, benign familial, 1; Alport syndr
- P69T (p.Pro69Thr), 1000Genomes rs199748684, ESP rs199748684, ExAC rs199748684, TOPMed rs199748684, REVEL 0.36, CADD 22.00
- P70L (p.Pro70Leu), ExAC rs751497878, gnomAD rs751497878, REVEL 0.27, CADD 10.80
- P70Q (p.Pro70Gln), ExAC rs751497878, gnomAD rs751497878, REVEL 0.30, CADD 17.60
- P70T (p.Pro70Thr), gnomAD rs1233036321, REVEL 0.30, CADD 14.20
- P72Q (p.Pro72Gln), TOPMed rs2061759035, REVEL 0.44, CADD 22.80, Uncertain significance, Inborn genetic diseases
- P72S (p.Pro72Ser), gnomAD rs1439965299, REVEL 0.37, CADD 22.20
- G74A (p.Gly74Ala), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- G74D (p.Gly74Asp), rs1320190484, NCI-TCGA Cosmic COSV1003, Ensembl rs1320190484, AlphaMissense 0.93, MetaLR 0.99, Variant assessed as somatic; moderate impact.
- P75T (p.Pro75Thr), Ensembl rs1011173875
- I76M (p.Ile76Met), rs1393470640, ClinGen CA350863428, ClinVar RCV001142918, ClinVar RCV003238839, REVEL 0.29, CADD 20.50, Uncertain significance, Alport syndrome; not provided; Benign familial hematuria
- I76T (p.Ile76Thr), TOPMed rs1334613513, gnomAD rs1334613513, REVEL 0.33, CADD 22.70
- I76V (p.Ile76Val), rs546883881, ClinGen CA66577379, ClinVar RCV003574024, 1000Genomes rs546883881, REVEL 0.28, CADD 20.80, Uncertain significance, not provided
- G77A (p.Gly77Ala), rs112204566, ClinGen CA350863420, ClinVar RCV001251515, Ensembl rs112204566, REVEL 0.89, CADD 24.00, Pathogenic, Benign familial hematuria
- G77E (p.Gly77Glu), Ensembl rs112204566, Pathogenic
- P78S (p.Pro78Ser), rs762682812, ClinGen CA2145738, ClinVar RCV001278689, ClinVar RCV001317669, REVEL 0.24, CADD 9.04, Conflicting interpretations, not provided; Autosomal recessive Alport syndrome; Benign familial hematuria
- P78T (p.Pro78Thr), ExAC rs762682812, TOPMed rs762682812, gnomAD rs762682812, REVEL 0.25, CADD 14.80, Uncertain significance, not provided
- L79M (p.Leu79Met), ExAC rs764905079, gnomAD rs764905079, REVEL 0.22, CADD 22.70
- L79V (p.Leu79Val), ExAC rs764905079, gnomAD rs764905079, REVEL 0.20, CADD 22.10
- L79S (p.Leu79Ser), gnomAD 2-227010314-A-G, CADD 0.03, SIFT 0.00
- G80E (p.Gly80Glu), rs1463746360, NCI-TCGA Cosmic COSV6163, gnomAD rs1463746360, AlphaMissense 0.87, MetaLR 0.99, Variant assessed as somatic; moderate impact.
- G80R (p.Gly80Arg), TOPMed rs1329673922, gnomAD rs1329673922, REVEL 0.92, CADD 25.10
- A81D (p.Ala81Asp), rs747022394, ClinGen CA2145734, ClinVar RCV001772497, ExAC rs747022394, REVEL 0.13, CADD 8.54, Uncertain significance, not provided
- A81T (p.Ala81Thr), TOPMed rs1371498491, gnomAD rs1371498491, REVEL 0.09, CADD 4.09
- A81V (p.Ala81Val), ExAC rs747022394, TOPMed rs747022394, gnomAD rs747022394, REVEL 0.08, CADD 6.61, Uncertain significance
- P82A (p.Pro82Ala), Ensembl rs2125037204, REVEL 0.32, CADD 17.60
- P82L (p.Pro82Leu), Ensembl rs2061756645, REVEL 0.35, CADD 22.20
- P82S (p.Pro82Ser), NCI-TCGA Cosmic COSV1003, MetaLR 0.82, MetaSVM 0.18, Variant assessed as somatic; moderate impact.
- G83A (p.Gly83Ala), Ensembl rs1559677316, REVEL 0.93, AlphaMissense 0.92, Likely pathogenic
- G83E (p.Gly83Glu), rs1559677316, ClinGen CA350863377, NCI-TCGA Cosmic COSV1003, NCI-TCGA Cosmic COSV6163, AlphaMissense 0.92, MetaLR 0.99, Conflicting interpretations, Alport syndrome; Autosomal recessive Alport syndrome; Hematuria, benign familial
- G83V (p.Gly83Val), NCI-TCGA Cosmic COSV1003, NCI-TCGA Cosmic COSV6163, MetaLR 0.99, MetaSVM 0.99, Variant assessed as somatic; moderate impact.
- I85T (p.Ile85Thr), ESP rs370260682, TOPMed rs370260682, REVEL 0.24, CADD 6.14, Uncertain significance, Autosomal recessive Alport syndrome; Hematuria, benign familial, 1
- G86R (p.Gly86Arg), ExAC rs776396958, gnomAD rs776396958, REVEL 0.98, CADD 26.00
- L87I (p.Leu87Ile), TOPMed rs1278670559
- S88L (p.Ser88Leu), rs1236298157, ClinGen CA350863346, ClinVar RCV003117964, TOPMed rs1236298157, REVEL 0.27, CADD 24.00, Uncertain significance, not provided
- E90D (p.Glu90Asp), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- E90V (p.Glu90Val), TOPMed rs2061755492, MetaLR 0.79, MetaSVM 0.64
- G92* (p.Gly92Ter), rs2061755379, ClinGen CA350863321, ClinVar RCV001264182, TOPMed rs2061755379, Likely pathogenic
- G92E (p.Gly92Glu), rs2125036772, ClinGen CA350863320, ClinVar RCV001371506, Ensembl rs2125036772, AlphaMissense 0.90, MetaLR 0.99, Uncertain significance, not provided
- M93T (p.Met93Thr), gnomAD rs1190123470, REVEL 0.16, CADD 16.30
- D96A (p.Asp96Ala), Ensembl rs2125036550, REVEL 0.36, CADD 23.20
- D96N (p.Asp96Asn), ExAC rs772710366, gnomAD rs772710366, REVEL 0.32, CADD 23.20, Uncertain significance, not provided
- R97C (p.Arg97Cys), rs202096172, ClinGen CA2145726, ClinVar RCV002624981, ClinVar RCV004538852, REVEL 0.42, CADD 15.40, Conflicting interpretations, not provided; COL4A4-related disorder
- R97H (p.Arg97His), rs769110804, NCI-TCGA Cosmic COSV6163, ExAC rs769110804, TOPMed rs769110804, REVEL 0.17, CADD 10.40, Uncertain significance, Inborn genetic diseases; not provided
- G98D (p.Gly98Asp), Ensembl rs2061753889, REVEL 0.92, CADD 24.50, Likely pathogenic, Alport syndrome
- G98S (p.Gly98Ser), ExAC rs780323761, TOPMed rs780323761, gnomAD rs780323761, REVEL 0.92, CADD 24.70, Likely pathogenic, Alport syndrome; Autosomal recessive Alport syndrome; Hematuria, benign familial
- P99A (p.Pro99Ala), rs2476238585, ClinGen CA2580065932, ClinVar RCV002838182, ClinVar RCV005027980, Pathogenic
- P99L (p.Pro99Leu), TOPMed rs1284690918, gnomAD rs1284690918, REVEL 0.17, CADD 0.63
- P99R (p.Pro99Arg), TOPMed rs1284690918, gnomAD rs1284690918, MetaLR 0.59, MetaSVM -0.37
- P99S (p.Pro99Ser), TOPMed rs1195937907, REVEL 0.20, CADD 12.80
- P100S (p.Pro100Ser), NCI-TCGA Cosmic COSV6163, MetaLR 0.90, MetaSVM 0.92, Variant assessed as somatic; moderate impact.
- G101* (p.Gly101Ter), rs2476237771, ClinGen CA350863254, ClinVar RCV003561566, Pathogenic
- G101E (p.Gly101Glu), Ensembl rs2125036152
- A102T (p.Ala102Thr), rs1353334452, ClinGen CA350863246, ClinVar RCV003725457, ClinVar RCV005323551, REVEL 0.29, CADD 18.40, Conflicting interpretations, Inborn genetic diseases; not provided
- A102V (p.Ala102Val), gnomAD rs1312002999, MetaLR 0.58, MetaSVM -0.32
- A103S (p.Ala103Ser), gnomAD rs1400862810, REVEL 0.21, CADD 16.40
- D105N (p.Asp105Asn), rs1434359218, ClinGen CA350863218, ClinVar RCV002831865, ClinVar RCV005616599, REVEL 0.22, CADD 22.10, Uncertain significance, Inborn genetic diseases
- K106R (p.Lys106Arg), rs1362665820, ClinGen CA350863199, ClinVar RCV002795432, ClinVar RCV005019400, REVEL 0.22, CADD 19.10, Uncertain significance, Hematuria, benign familial, 1; Autosomal recessive Alport syndrome; not provided
- G107E (p.Gly107Glu), ESP rs375164188, TOPMed rs375164188
- D108A (p.Asp108Ala), NCI-TCGA TCGA novel, MetaLR 0.79, MetaSVM 0.52, Variant assessed as somatic; moderate impact.
- K109=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- K109R (p.Lys109Arg), ExAC rs750519151, REVEL 0.34, CADD 31.00
- G110=, NCI-TCGA Cosmic COSV6163, Variant assessed as somatic; low impact.
- G110A (p.Gly110Ala), gnomAD rs1370340334, REVEL 0.94, CADD 28.00
Public COL4A4 analysis runs
- COL4A4 analysis run — COL4A4 (2,719 variants) — completed 2026-08-19