COL3A1 (Collagen alpha-1(III) chain) variants and mutations
COL3A1 (also known as Collagen alpha-1(III) chain) is a human protein-coding gene encoding a collagen alpha-1(III) chain protein. Its type III collagen fibrils provide tensile support in arteries, bowel, uterus, skin, and other distensible connective tissues. Pathogenic variants cause vascular Ehlers-Danlos syndrome with marked arterial and hollow-organ fragility. This analysis covers 2,735 COL3A1 variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes Ehlers-Danlos syndrome, vascular type, polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, and autosomal dominant Ehlers-Danlos syndrome, vascular type. Example COL3A1 variants include M1L, M2T, and M2V.
Variant analysis overview
- Gene: COL3A1
- Protein: Collagen alpha-1(III) chain
- UniProt accession: P02461
- Organism: Homo sapiens
- Variants analyzed: 2735
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,567 unspecified-consequence records; 66 missense variants; 85 synonymous variants; 3 in-frame deletions; 4 frameshift variants; 3 stop-gained variants; 2 splice-region variants; 5 substitution
- Prediction scores: 2,144 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Ehlers-Danlos syndrome, vascular type, polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, autosomal dominant Ehlers-Danlos syndrome, vascular type, familial thoracic aortic aneurysm and aortic dissection, Ehlers-Danlos syndrome, Dupuytren Contracture, Rare disease with thoracic aortic aneurysm and aortic dissection, Familial hemophagocytic lymphohistiocytosis, Abnormality of the cardiovascular system, Skin ulcer, eye disorder, Aortic dissection.
Protein structure and variant hotspots
- Protein features: 2 domains; 5 binding sites; 151 post-translational modification sites.
- Structural context: 498 variants have structural context.
- PTM context: 260 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, ClinGen, MaveDB, LitVar.
Notable COL3A1 variants
Examples include M1L, M2T, M2V, M2L, M2R, M2K, S3R, S3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs1687765120, ClinGen CA349845330, ClinVar RCV001231945, MetaLR 0.79, MetaSVM 0.74, Uncertain significance, Ehlers-Danlos syndrome, type 4
- M2T (p.Met2Thr), Ensembl rs1687765186, REVEL 0.34, MetaLR 0.48
- M2V (p.Met2Val), gnomAD 2-188974493-A-G, REVEL 0.38, CADD 21.20
- M2L (p.Met2Leu), gnomAD 2-188974493-A-T, REVEL 0.38, CADD 21.00
- M2R (p.Met2Arg), gnomAD 2-188974494-T-G, REVEL 0.53, CADD 21.00
- M2K (p.Met2Lys), gnomAD 2-188974494-T-A, REVEL 0.48, CADD 20.40
- S3R (p.Ser3Arg), rs2153500007, ClinGen CA349845353, ClinVar RCV002383130, Ensembl rs2153500007, AlphaMissense 0.84, MetaLR 0.81, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- S3S (p.Ser3Ser), gnomAD 2-188974498-C-T, CADD 14.50
- F4C (p.Phe4Cys), ExAC rs766299663, gnomAD rs766299663, REVEL 0.47, MetaLR 0.59
- F4V (p.Phe4Val), NCI-TCGA TCGA novel, MetaLR 0.57, MetaSVM 0.07, Variant assessed as somatic; moderate impact.
- V5E (p.Val5Glu), rs751315184, ClinGen CA074376, ClinVar RCV001911406, ClinVar RCV003438891, REVEL 0.70, MetaLR 0.79, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Da
- V5M (p.Val5Met), rs1461198652, ClinGen CA349845362, ClinVar RCV000507209, ClinVar RCV000702640, REVEL 0.58, MetaLR 0.81, Uncertain significance, not provided; not specified; Ehlers-Danlos syndrome, type 4
- V5L (p.Val5Leu), gnomAD 2-188974502-G-C, REVEL 0.57, CADD 25.30
- V5V (p.Val5Val), gnomAD 2-188974504-G-C, CADD 12.70
- Q6* (p.Gln6Ter), Ensembl rs1687765513
- Q6H (p.Gln6His), rs892404442, ClinGen CA349845373, ClinVar RCV003095544, ClinVar RCV005323345, REVEL 0.58, MetaLR 0.57, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Danlos syndrome
- Q6P (p.Gln6Pro), gnomAD rs1296702474, REVEL 0.59, MetaLR 0.54
- Q6Q (p.Gln6Gln), rs892404442, gnomAD 2-188974507-A-G, CADD 13.00
- K7N (p.Lys7Asn), Ensembl rs1576455552
- K7R (p.Lys7Arg), Ensembl rs1576455551, MetaLR 0.50, MetaSVM -0.49
- K7K (p.Lys7Lys), gnomAD 2-188974510-G-A, CADD 13.00
- G8E (p.Gly8Glu), rs2153500011, ClinGen CA349845386, NCI-TCGA Cosmic COSV5859, cosmic curated COSV58597, REVEL 0.48, MetaLR 0.43, Uncertain significance, not provided; Ehlers-Danlos syndrome, type 4
- G8R (p.Gly8Arg), rs1687765852, ClinGen CA349845383, ClinVar RCV001890835, Ensembl rs1687765852, AlphaMissense 0.52, MetaLR 0.40, Uncertain significance, Ehlers-Danlos syndrome, type 4
- G8G (p.Gly8Gly), gnomAD 2-188974513-G-C, CADD 12.30
- S9A (p.Ser9Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- S9T (p.Ser9Thr), Ensembl rs1576455561, MetaLR 0.31, MetaSVM -0.80
- S9G (p.Ser9Gly), gnomAD 2-188974514-A-G, REVEL 0.30, MetaLR 0.52
- W10* (p.Trp10Ter), rs587779677, ClinGen CA006034, ClinVar RCV000087673, ClinVar RCV006277707, CADD 38.00, Pathogenic
- W10C (p.Trp10Cys), rs587779677, ClinGen CA349845403, ClinVar RCV004007992, Uncertain significance, Ehlers-Danlos syndrome, type 4
- L12R (p.Leu12Arg), 1000Genomes rs2153500015, REVEL 0.63, MetaLR 0.60
- L12F (p.Leu12Phe), gnomAD 2-188974523-C-T, REVEL 0.29, MetaLR 0.48
- L12H (p.Leu12His), gnomAD 2-188974524-T-A, REVEL 0.61, MetaLR 0.66
- L12L (p.Leu12Leu), rs781047496, gnomAD 2-188974525-T-G, CADD 12.40
- L13F (p.Leu13Phe), gnomAD rs1303302149, REVEL 0.27, MetaLR 0.61
- L13P (p.Leu13Pro), rs2153500016, ClinGen CA349845420, ClinVar RCV001756507, Ensembl rs2153500016, AlphaMissense 0.44, MetaLR 0.74, Uncertain significance, not provided
- L13L (p.Leu13Leu), rs1343634872, gnomAD 2-188974528-C-A, CADD 4.76
- A14G (p.Ala14Gly), rs1231364424, ClinGen CA349845424, ClinVar RCV001179685, ClinVar RCV004006593, REVEL 0.33, MetaLR 0.56, Uncertain significance, Ehlers-Danlos syndrome, type 4; Familial thoracic aortic aneurysm and aortic dis
- A14P (p.Ala14Pro), rs547373542, ClinGen CA349845422, ClinVar RCV004012678, AlphaMissense 0.12, MetaLR 0.48, Uncertain significance, Ehlers-Danlos syndrome, type 4
- A14S (p.Ala14Ser), rs547373542, ClinGen CA076453, ClinVar RCV001183081, ClinVar RCV004008349, REVEL 0.24, AlphaMissense 0.12, Uncertain significance, Ehlers-Danlos syndrome, type 4; Familial thoracic aortic aneurysm and aortic dis
- A14T (p.Ala14Thr), rs547373542, ClinGen CA62577062, ClinVar RCV001177894, ClinVar RCV002290616, REVEL 0.21, AlphaMissense 0.12, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; not provided; Ehlers-Da
- A14A (p.Ala14Ala), rs1576455600, gnomAD 2-188974531-T-C, CADD 14.10
- L15V (p.Leu15Val), rs1278335125, ClinGen CA349845427, ClinVar RCV003633316, TOPMed rs1278335125, REVEL 0.18, MetaLR 0.38, Uncertain significance, Ehlers-Danlos syndrome, type 4
- L15L (p.Leu15Leu), gnomAD 2-188974532-C-T, CADD 13.10
- L16F (p.Leu16Phe), cosmic curated COSV10735, NCI-TCGA TCGA novel, Uncertain significance, Ehlers-Danlos syndrome, type 4
- L16R (p.Leu16Arg), ESP rs373953505, TOPMed rs373953505, MetaLR 0.48, MetaSVM -0.14
- H17L (p.His17Leu), rs1311785540, ClinGen CA349845441, ClinVar RCV001187073, ClinVar RCV001337496, REVEL 0.32, MetaLR 0.47, Uncertain significance, Ehlers-Danlos syndrome, type 4; Familial thoracic aortic aneurysm and aortic dis
- H17P (p.His17Pro), TOPMed rs1311785540, gnomAD rs1311785540, REVEL 0.39, MetaLR 0.56, Uncertain significance
- P18H (p.Pro18His), NCI-TCGA Cosmic COSV5858, cosmic curated COSV58584, Variant assessed as somatic; moderate impact.
- P18R (p.Pro18Arg), rs1687767062, ClinGen CA349845447, ClinVar RCV002618001, TOPMed rs1687767062, REVEL 0.58, MetaLR 0.65, Uncertain significance, Ehlers-Danlos syndrome, type 4
- P18S (p.Pro18Ser), rs886038951, ClinGen CA10587522, ClinVar RCV002310866, Ensembl rs886038951, AlphaMissense 0.08, MetaLR 0.47, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- P18P (p.Pro18Pro), rs777129787, gnomAD 2-188974543-C-T, CADD 13.90
- T19A (p.Thr19Ala), rs1300339107, ClinGen CA349845449, ClinVar RCV000793216, ClinVar RCV001187007, REVEL 0.22, AlphaMissense 0.10, Uncertain significance, not specified; Familial thoracic aortic aneurysm and aortic dissection; Ehlers-D
- T19P (p.Thr19Pro), rs1300339107, ClinGen CA349845450, ClinVar RCV004013489, TOPMed rs1300339107, REVEL 0.46, AlphaMissense 0.10, Uncertain significance, Ehlers-Danlos syndrome, type 4
- T19S (p.Thr19Ser), rs1300339107, ClinGen CA349845451, ClinVar RCV002796601, ClinVar RCV003528413, AlphaMissense 0.10, MetaLR 0.44, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Danlos syndrome
- T19T (p.Thr19Thr), gnomAD 2-188974546-T-C, CADD 13.50
- I20L (p.Ile20Leu), TOPMed rs1342128671, MetaLR 0.31, MetaSVM -0.69, Likely benign
- I20V (p.Ile20Val), rs1342128671, ClinGen CA349845457, NCI-TCGA Cosmic COSV5859, cosmic curated COSV58595, REVEL 0.33, MetaLR 0.33, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Danlos syndrome
- I21N (p.Ile21Asn), rs1296337954, ClinGen CA349845465, ClinVar RCV003634847, AlphaMissense 0.30, MetaLR 0.54, Uncertain significance, not provided; Ehlers-Danlos syndrome, type 4
- I21T (p.Ile21Thr), TOPMed rs1296337954, REVEL 0.23, AlphaMissense 0.30
- I21del (p.Ile21del), gnomAD 2-188974545-CTAT-, CADD 18.00
- I21V (p.Ile21Val), gnomAD 2-188974550-A-G, REVEL 0.20, MetaLR 0.43
- L22W (p.Leu22Trp), Ensembl rs2153500022
- A23V (p.Ala23Val), NCI-TCGA TCGA novel, MetaLR 0.73, MetaSVM 0.38, Variant assessed as somatic; moderate impact.
- Q24R (p.Gln24Arg), gnomAD 2-188974560-A-G, REVEL 0.51, MetaLR 0.75
- Q25* (p.Gln25Ter), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10048, Variant assessed as somatic; high impact.
- Q25P (p.Gln25Pro), ExAC rs748787122, gnomAD rs748787122, REVEL 0.58, MetaLR 0.76, Uncertain significance, Ehlers-Danlos syndrome, type 4; not provided
- Q25R (p.Gln25Arg), rs748787122, ClinGen CA62577079, ClinVar RCV001187218, ClinVar RCV002559122, REVEL 0.44, MetaLR 0.75, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Danlos syndrome
- Q25Q (p.Gln25Gln), gnomAD 2-188974564-G-A, CADD 12.30
- E26G (p.Glu26Gly), rs1399291719, ClinGen CA349845501, ClinVar RCV002409894, ClinVar RCV006469822, REVEL 0.19, MetaLR 0.44, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Danlos syndrome
- E26K (p.Glu26Lys), TOPMed rs1687767912, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- E26Q (p.Glu26Gln), rs1687767912, ClinGen CA349845497, ClinVar RCV001175532, TOPMed rs1687767912, AlphaMissense 0.08, MetaLR 0.38, Uncertain significance, not specified
- A27D (p.Ala27Asp), rs759521597, ClinGen CA349846776, ClinVar RCV001184192, ExAC rs759521597, AlphaMissense 0.07, MetaLR 0.39, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- A27G (p.Ala27Gly), rs759521597, ClinGen CA076965, ClinVar RCV004013891, ExAC rs759521597, REVEL 0.14, AlphaMissense 0.07, Uncertain significance, Ehlers-Danlos syndrome, type 4
- A27T (p.Ala27Thr), TOPMed rs1687768073, MetaLR 0.51, MetaSVM -0.43
- V28F (p.Val28Phe), NCI-TCGA TCGA novel, MetaLR 0.44, MetaSVM -0.62, Variant assessed as somatic; moderate impact.
- V28L (p.Val28Leu), ExAC rs767509336, gnomAD rs767509336, REVEL 0.21, MetaLR 0.35
- V28A (p.Val28Ala), gnomAD 2-188984763-T-C, REVEL 0.16, MetaLR 0.37
- V28V (p.Val28Val), rs752574994, gnomAD 2-188984764-T-C, CADD 6.75
- E29D (p.Glu29Asp), rs760482912, ClinGen CA077021, ClinVar RCV001176571, ClinVar RCV002558824, REVEL 0.20, MetaLR 0.30, Conflicting interpretations, not provided; Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Da
- E29del (p.Glu29del), rs1559052566, gnomAD 2-188984764-TGAA-, CADD 14.80
- E29K (p.Glu29Lys), gnomAD 2-188984765-G-A, REVEL 0.33, MetaLR 0.41
- E29G (p.Glu29Gly), gnomAD 2-188984766-A-G, REVEL 0.18, MetaLR 0.46
- E29E (p.Glu29Glu), gnomAD 2-188984767-A-G, CADD 2.03
- G30E (p.Gly30Glu), TOPMed rs1688028911, REVEL 0.07, MetaLR 0.12
- G30R (p.Gly30Arg), rs530070719, NCI-TCGA Cosmic COSV5858, cosmic curated COSV58584, 1000Genomes rs530070719, AlphaMissense 0.13, MetaLR 0.21, Variant assessed as somatic; moderate impact.
- G30V (p.Gly30Val), NCI-TCGA TCGA novel, MetaLR 0.17, MetaSVM -0.99, Variant assessed as somatic; moderate impact.
- G30G (p.Gly30Gly), rs753517892, gnomAD 2-188984770-A-C, CADD 11.30
- G31E (p.Gly31Glu), ExAC rs778455518, REVEL 0.26, MetaLR 0.20
- G31R (p.Gly31Arg), rs374537884, ClinGen CA077075, ClinVar RCV000634724, ClinVar RCV001525097, REVEL 0.36, MetaLR 0.28, Conflicting interpretations, not specified; Ehlers-Danlos syndrome, type 4; Familial thoracic aortic aneurysm
- G31V (p.Gly31Val), gnomAD 2-188984772-G-T, REVEL 0.37, MetaLR 0.24
- G31G (p.Gly31Gly), gnomAD 2-188984773-A-G, CADD 14.30
- C32F (p.Cys32Phe), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10048, Variant assessed as somatic; moderate impact.
- C32Y (p.Cys32Tyr), rs2153501342, ClinGen CA349846823, ClinVar RCV001768715, Ensembl rs2153501342, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, not provided
- C32C (p.Cys32Cys), rs1296448513, gnomAD 2-188984776-T-C, CADD 12.20
- S33A (p.Ser33Ala), gnomAD 2-188984777-T-G, REVEL 0.06, MetaLR 0.19
- H34R (p.His34Arg), rs752110396, ClinGen CA004024, ClinVar RCV000181120, ClinVar RCV000709845, REVEL 0.31, MetaLR 0.30, Uncertain significance, not provided; Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Da
- L35F (p.Leu35Phe), ESP rs368703012, TOPMed rs368703012, gnomAD rs368703012, REVEL 0.25, MetaLR 0.35, Uncertain significance
- L35I (p.Leu35Ile), rs368703012, ClinGen CA349846848, ClinVar RCV001907873, ClinVar RCV002276918, REVEL 0.22, MetaLR 0.28, Uncertain significance, Ehlers-Danlos syndrome, type 4; Ehlers-Danlos syndrome; Familial thoracic aortic
- L35V (p.Leu35Val), ESP rs368703012, TOPMed rs368703012, gnomAD rs368703012, REVEL 0.20, MetaLR 0.29, Uncertain significance
- Q37E (p.Gln37Glu), rs2469105633, ClinGen CA349846866, ClinVar RCV004014757, Uncertain significance, Ehlers-Danlos syndrome, type 4
- Q37H (p.Gln37His), rs2153501346, ClinGen CA349846874, ClinVar RCV001811785, ClinVar RCV003120695, AlphaMissense 0.33, MetaLR 0.45, Uncertain significance, Ehlers-Danlos syndrome, type 4; not provided
- Q37K (p.Gln37Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q37L (p.Gln37Leu), rs1060500205, ClinGen CA16610630, cosmic curated COSV58582, ClinVar RCV000459602, AlphaMissense 0.20, MetaLR 0.44, Uncertain significance, Ehlers-Danlos syndrome, type 4
- Q37Q (p.Gln37Gln), gnomAD 2-188984791-G-A, CADD 10.10
- S38F (p.Ser38Phe), ExAC rs755509578, gnomAD rs755509578, REVEL 0.10, MetaLR 0.15, Uncertain significance
- S38Y (p.Ser38Tyr), rs755509578, ClinGen CA349846881, ClinVar RCV002012109, ExAC rs755509578, REVEL 0.07, MetaLR 0.18, Uncertain significance, Ehlers-Danlos syndrome, type 4
- S38P (p.Ser38Pro), gnomAD 2-188984792-T-C, REVEL 0.23, MetaLR 0.15
- S38S (p.Ser38Ser), rs141241764, gnomAD 2-188984794-C-G, CADD 9.32
- Y39* (p.Tyr39Ter), rs2469105653, ClinGen CA349846893, ClinVar RCV002510237, Likely pathogenic
- Y39C (p.Tyr39Cys), gnomAD 2-188984796-A-G, REVEL 0.83, MetaLR 0.76
- A40E (p.Ala40Glu), 1000Genomes rs201380807, ExAC rs201380807, TOPMed rs201380807, gnomAD rs201380807, REVEL 0.07, MetaLR 0.19, Uncertain significance
- A40G (p.Ala40Gly), rs201380807, ClinGen CA349846899, ClinVar RCV001187824, ClinVar RCV001862964, REVEL 0.11, MetaLR 0.23, Uncertain significance, Ehlers-Danlos syndrome, type 4; Familial thoracic aortic aneurysm and aortic dis
- A40T (p.Ala40Thr), rs763720540, ClinGen CA073909, ClinVar RCV001186553, ClinVar RCV003633573, REVEL 0.14, MetaLR 0.24, Uncertain significance, Ehlers-Danlos syndrome, type 4; Familial thoracic aortic aneurysm and aortic dis
- A40V (p.Ala40Val), rs201380807, ClinGen CA004121, cosmic curated COSV10048, ClinVar RCV000181046, REVEL 0.22, MetaLR 0.23, Conflicting interpretations, Connective tissue disorder; not specified; not provided
- A40A (p.Ala40Ala), rs138115610, gnomAD 2-188984800-G-A, CADD 5.78
- D41N (p.Asp41Asn), rs794728035, ClinGen CA10587524, ClinVar RCV001207845, ClinVar RCV002311115, REVEL 0.15, MetaLR 0.18, Uncertain significance, Ehlers-Danlos syndrome, type 4; Familial thoracic aortic aneurysm and aortic dis
- D41Y (p.Asp41Tyr), rs794728035, ClinGen CA004135, ClinVar RCV001185489, ClinVar RCV001721132, REVEL 0.34, MetaLR 0.51, Uncertain significance, not provided; Polymicrogyria with or without vascular-type Ehlers-Danlos syndrom
- D41V (p.Asp41Val), gnomAD 2-188984802-A-T, REVEL 0.33, MetaLR 0.35
- D41D (p.Asp41Asp), rs770961095, gnomAD 2-188984803-T-C, CADD 11.80
- R42S (p.Arg42Ser), rs2469105686, ClinGen CA349846918, ClinVar RCV004528749, Uncertain significance, COL3A1-related disorder
- R42T (p.Arg42Thr), TOPMed rs1304206848, gnomAD rs1304206848, REVEL 0.29, MetaLR 0.31
- R42R (p.Arg42Arg), gnomAD 2-188984804-A-C, CADD 13.10
- D43H (p.Asp43His), NCI-TCGA Cosmic COSV5858, cosmic curated COSV58582, MetaLR 0.60, MetaSVM 0.44, Variant assessed as somatic; moderate impact.
- D43D (p.Asp43Asp), rs774591764, gnomAD 2-188984809-T-C, CADD 11.10
- V44I (p.Val44Ile), rs79632685, ClinGen CA004218, ClinVar RCV000226945, ClinVar RCV001183976, REVEL 0.27, MetaLR 0.47, Likely benign, not specified; not provided; Familial thoracic aortic aneurysm and aortic dissec
- V44L (p.Val44Leu), 1000Genomes rs79632685, ESP rs79632685, ExAC rs79632685, TOPMed rs79632685, REVEL 0.55, MetaLR 0.60, Likely benign
- W45* (p.Trp45Ter), rs1559052609, ClinGen CA349846946, ClinVar RCV000697608, Ensembl rs1559052609, Pathogenic
- P47T (p.Pro47Thr), TOPMed rs1367864085, MetaLR 0.63, MetaSVM 0.37
- P47L (p.Pro47Leu), gnomAD 2-188984820-C-T, REVEL 0.80, MetaLR 0.61
- E48D (p.Glu48Asp), rs1199014910, ClinGen CA349846988, ClinVar RCV003633450, Uncertain significance, Ehlers-Danlos syndrome, type 4
- E48E (p.Glu48Glu), rs1199014910, gnomAD 2-188984824-A-G, CADD 12.10
- P49A (p.Pro49Ala), rs1234344050, ClinGen CA349846991, ClinVar RCV000758212, ClinVar RCV000853487, REVEL 0.43, MetaLR 0.45, Likely pathogenic, Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome; Ehlers-Danl
- P49L (p.Pro49Leu), ExAC rs775512273, gnomAD rs775512273, REVEL 0.59, MetaLR 0.59
- P49P (p.Pro49Pro), gnomAD 2-188984827-A-G, CADD 8.70
- C50* (p.Cys50Ter), rs559102186, ClinGen CA349847006, ClinVar RCV003022385, CADD 35.00, Pathogenic
- C50S (p.Cys50Ser), rs2469105718, ClinGen CA349847003, ClinVar RCV003523230, Uncertain significance, Ehlers-Danlos syndrome, type 4
- C50C (p.Cys50Cys), rs559102186, gnomAD 2-188984830-C-T, CADD 12.60
- Q51Q (p.Gln51Gln), gnomAD 2-188984833-A-G, CADD 12.60
- I52M (p.Ile52Met), rs2469105728, ClinGen CA349847033, ClinVar RCV003818162, Uncertain significance, Ehlers-Danlos syndrome, type 4
- V54F (p.Val54Phe), cosmic curated COSV10439, gnomAD rs1425860292
- V54I (p.Val54Ile), NCI-TCGA Cosmic COSV1043, NCI-TCGA Cosmic COSV5858, cosmic curated COSV58582, gnomAD rs1425860292, MetaLR 0.26, MetaSVM -0.70, Uncertain significance, Ehlers-Danlos syndrome, type 4
- V54V (p.Val54Val), rs1481129837, gnomAD 2-188984842-C-T, CADD 12.70
- D56E (p.Asp56Glu), NCI-TCGA TCGA novel, MetaLR 0.46, MetaSVM -0.15, Variant assessed as somatic; moderate impact.
- D56N (p.Asp56Asn), rs1173687812, ClinGen CA349847068, ClinVar RCV003068230, ClinVar RCV005403278, REVEL 0.53, MetaLR 0.53, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Danlos syndrome
- S57S (p.Ser57Ser), rs1688031065, gnomAD 2-188984851-A-G, CADD 13.30
- S59A (p.Ser59Ala), rs1553506856, ClinGen CA349847102, ClinVar RCV000499758, Ensembl rs1553506856, REVEL 0.11, MetaLR 0.17, Uncertain significance, not specified
- S59S (p.Ser59Ser), rs1404878392, gnomAD 2-188984857-C-T, CADD 10.20
- V60I (p.Val60Ile), rs762028131, ClinGen CA074644, NCI-TCGA Cosmic COSV5858, cosmic curated COSV58584, REVEL 0.28, AlphaMissense 0.07, Uncertain significance, not specified; not provided; Familial thoracic aortic aneurysm and aortic dissec
- V60L (p.Val60Leu), rs762028131, ClinGen CA349847111, ClinVar RCV004012321, AlphaMissense 0.07, MetaLR 0.30, Uncertain significance, Ehlers-Danlos syndrome, type 4
- V60F (p.Val60Phe), gnomAD 2-188984858-G-T, REVEL 0.72, MetaLR 0.71
- V60A (p.Val60Ala), gnomAD 2-188984859-T-C, REVEL 0.57, MetaLR 0.52
- L61I (p.Leu61Ile), NCI-TCGA Cosmic COSV5858, cosmic curated COSV58584, MetaLR 0.44, MetaSVM -0.34, Variant assessed as somatic; moderate impact.
- L61L (p.Leu61Leu), rs753474870, gnomAD 2-188984863-C-T, CADD 12.30
- C62C (p.Cys62Cys), rs764749176, gnomAD 2-188984866-C-T, CADD 4.87
- D63N (p.Asp63Asn), rs1688031625, ClinGen CA349847138, NCI-TCGA Cosmic COSV5858, cosmic curated COSV58587, REVEL 0.48, MetaLR 0.58, Uncertain significance, Ehlers-Danlos syndrome, type 4; Familial thoracic aortic aneurysm and aortic dis
- D63D (p.Asp63Asp), gnomAD 2-188984869-T-C, CADD 13.20
- D64H (p.Asp64His), Ensembl rs1688031667, REVEL 0.49, MetaLR 0.46
- D64N (p.Asp64Asn), gnomAD 2-188984870-G-A, REVEL 0.28, MetaLR 0.31
- I65T (p.Ile65Thr), rs1050728178, ClinGen CA62585446, ClinVar RCV001191755, ClinVar RCV006465698, REVEL 0.49, MetaLR 0.34, Uncertain significance, Ehlers-Danlos syndrome, type 4; Familial thoracic aortic aneurysm and aortic dis
- I65V (p.Ile65Val), rs1440480352, ClinGen CA349847164, ClinVar RCV001227423, ClinVar RCV001806062, REVEL 0.09, MetaLR 0.14, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Danlos syndrome
- I65L (p.Ile65Leu), gnomAD 2-188984873-A-T, REVEL 0.21, MetaLR 0.27
- I66L (p.Ile66Leu), rs2153501357, ClinGen CA349847169, ClinVar RCV001525997, ClinVar RCV001873685, REVEL 0.12, MetaLR 0.25, Uncertain significance, Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome; Ehlers-Danl
- I66M (p.Ile66Met), rs372269408, ClinGen CA074891, cosmic curated COSV58582, ClinVar RCV000634706, REVEL 0.13, MetaLR 0.21, Conflicting interpretations, not provided; Familial thoracic aortic aneurysm and aortic dissection; not speci
- I66R (p.Ile66Arg), rs2469106201, ClinGen CA349847174, ClinVar RCV004016552, Uncertain significance, Ehlers-Danlos syndrome, type 4
- I66I (p.Ile66Ile), rs372269408, gnomAD 2-188984878-A-T, CADD 10.10
- C67S (p.Cys67Ser), rs1085307576, ClinGen CA349847185, ClinVar RCV000489656, Ensembl rs1085307576, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, not provided
- D68E (p.Asp68Glu), rs368299739, ClinGen CA349847199, ClinVar RCV001192004, ESP rs368299739, AlphaMissense 0.20, MetaLR 0.06, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- D68G (p.Asp68Gly), rs376603102, ClinGen CA004922, ClinVar RCV000541054, ClinVar RCV000709865, REVEL 0.30, MetaLR 0.22, Uncertain significance, Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome; Ehlers-Danl
- D68H (p.Asp68His), gnomAD 2-188984882-G-C, REVEL 0.30, MetaLR 0.34
- D68D (p.Asp68Asp), rs368299739, gnomAD 2-188984884-C-T, AlphaMissense 0.20, MetaLR 0.06
- D69H (p.Asp69His), rs112714742, ClinGen CA349847203, ClinVar RCV004009898, 1000Genomes rs112714742, REVEL 0.36, MetaLR 0.49, Uncertain significance, Ehlers-Danlos syndrome, type 4
- D69N (p.Asp69Asn), rs112714742, ClinGen CA074965, cosmic curated COSV58596, ClinVar RCV002018184, REVEL 0.25, MetaLR 0.33, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection; Ehlers-Danlos syndrome
- D69Y (p.Asp69Tyr), rs112714742, ClinGen CA349847204, ClinVar RCV001189701, 1000Genomes rs112714742, REVEL 0.48, MetaLR 0.57, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- Q70R (p.Gln70Arg), rs2153501359, ClinGen CA349847216, ClinVar RCV001525156, Ensembl rs2153501359, AlphaMissense 0.08, MetaLR 0.16, Uncertain significance, Familial thoracic aortic aneurysm and aortic dissection
- E71K (p.Glu71Lys), gnomAD rs1688032354, REVEL 0.05, MetaLR 0.07
- L72S (p.Leu72Ser), ExAC rs756472145, gnomAD rs756472145, REVEL 0.28, MetaLR 0.30
- L72L (p.Leu72Leu), rs1688032482, gnomAD 2-188984896-A-G, CADD 12.60
- D73G (p.Asp73Gly), rs2469106248, ClinGen CA349847250, ClinVar RCV004008144, Uncertain significance, Ehlers-Danlos syndrome, type 4
- D73H (p.Asp73His), rs200246388, ClinGen CA075056, cosmic curated COSV58594, ClinVar RCV000264796, REVEL 0.54, MetaLR 0.49, Conflicting interpretations, not specified; Ehlers-Danlos syndrome; not provided
- D73D (p.Asp73Asp), rs886038228, gnomAD 2-188984899-C-T, CADD 11.20
Public COL3A1 analysis runs
- COL3A1 analysis run — COL3A1 (2,735 variants) — completed 2026-08-18