NOTCH3 (Q9UM47) variants and mutations
NOTCH3 (also known as Q9UM47) is a human protein-coding gene encoding a neurogenic locus notch homolog protein 3 protein. Its signaling helps maintain vascular smooth-muscle and mural-cell identity in small arteries. Pathogenic cysteine-altering variants cause CADASIL, with migraine, recurrent ischemic strokes, white-matter disease, and progressive cognitive impairment. This analysis covers 5,573 NOTCH3 variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen, CADASIL, and lateral meningocele syndrome. Example NOTCH3 variants include M1K, P3L, and G4R.
Variant analysis overview
- Gene: NOTCH3
- Protein: Q9UM47
- UniProt accession: Q9UM47
- Organism: Homo sapiens
- Variants analyzed: 5573
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 5,087 unspecified-consequence records; 155 synonymous variants; 278 missense variants; 27 frameshift variants; 15 stop-gained variants; 1 protein altering variant; 1 in-frame insertions; 3 in-frame deletions; 6 substitution
- Prediction scores: 4,376 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen, CADASIL, lateral meningocele syndrome, myofibromatosis, infantile, 2, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, neurodevelopmental disorder, leukodystrophy, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoe, ischemic stroke, migraine with aura, infantile myofibromatosis, migraine disorder.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 34 domains; 4 post-translational modification sites.
- Structural context: 3,037 variants have structural context.
- PTM context: 15 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 NOTCH3 variants
Examples include M1K, P3L, G4R, R6C, R6H, G7A, R8H, R8P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1K (p.Met1Lys), rs2047007942, ClinGen CA404483703, ClinVar RCV001122241, MetaLR 0.32, MetaSVM -0.67, Uncertain significance, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen
- P3L (p.Pro3Leu), TOPMed rs1214845572, gnomAD rs1214845572, REVEL 0.17, CADD 23.00, Conflicting interpretations, not specified; not provided
- G4R (p.Gly4Arg), TOPMed rs1271542688, REVEL 0.25, CADD 22.00, Uncertain significance, not provided
- R6C (p.Arg6Cys), TOPMed rs1189616145, gnomAD rs1189616145, REVEL 0.29, CADD 24.00
- R6H (p.Arg6His), TOPMed rs1198745617, REVEL 0.22, CADD 22.40
- G7A (p.Gly7Ala), Ensembl rs2145457828, MetaLR 0.19, MetaSVM -0.94
- R8H (p.Arg8His), Ensembl rs1448789814, REVEL 0.12, CADD 23.00
- R8P (p.Arg8Pro), Ensembl rs1448789814, MetaLR 0.21, MetaSVM -0.94
- R9P (p.Arg9Pro), Ensembl rs2145457814, MetaLR 0.17, MetaSVM -0.96
- R10H (p.Arg10His), rs2047007730, ClinGen CA404483646, ClinVar RCV003093369, ClinVar RCV005377265, REVEL 0.36, CADD 18.60, Uncertain significance, Inborn genetic diseases; not provided
- R10P (p.Arg10Pro), TOPMed rs2047007730, MetaLR 0.72, MetaSVM 0.21, Uncertain significance
- R11P (p.Arg11Pro), Ensembl rs2145457794, MetaLR 0.73, MetaSVM 0.16
- R12G (p.Arg12Gly), TOPMed rs2047007706
- R12H (p.Arg12His), Ensembl rs2047007605, REVEL 0.33, CADD 21.60
- R13C (p.Arg13Cys), rs2512676498, ClinGen CA404483629, ClinVar RCV003011721, REVEL 0.33, CADD 20.90, Uncertain significance, not provided
- P14L (p.Pro14Leu), Ensembl rs2145457718, REVEL 0.25, CADD 10.70
- M15V (p.Met15Val), Ensembl rs2145457710, REVEL 0.30, CADD 15.50
- S16A (p.Ser16Ala), Ensembl rs2145457704
- S16L (p.Ser16Leu), Ensembl rs2047007519, REVEL 0.28, CADD 15.10
- P19A (p.Pro19Ala), ExAC rs778680746, gnomAD rs778680746, REVEL 0.36, CADD 8.55
- P19L (p.Pro19Leu), gnomAD rs1273312264, REVEL 0.31, CADD 10.80
- P20A (p.Pro20Ala), 1000Genomes rs2145457639, REVEL 0.45, CADD 14.40
- P20S (p.Pro20Ser), rs2145457639, ClinGen CA404483585, ClinVar RCV004488246, REVEL 0.40, CADD 16.40, Uncertain significance, Inborn genetic diseases
- P21S (p.Pro21Ser), rs1438796675, ClinGen CA404483579, ClinVar RCV002471895, ClinVar RCV002569381, REVEL 0.37, CADD 20.50, Uncertain significance, not provided; Inborn genetic diseases; Cerebral arteriopathy, autosomal dominant
- P23S (p.Pro23Ser), gnomAD rs1350683833, REVEL 0.22, CADD 6.95
- V24G (p.Val24Gly), TOPMed rs1387194156, gnomAD rs1387194156, REVEL 0.39, CADD 17.30
- V24M (p.Val24Met), TOPMed rs2047007209, REVEL 0.21, CADD 12.70
- R25G (p.Arg25Gly), gnomAD rs1331168157
- R25Q (p.Arg25Gln), TOPMed rs2047007114, REVEL 0.49, CADD 18.70
- R25W (p.Arg25Trp), gnomAD rs1331168157, REVEL 0.39, CADD 17.40
- A26S (p.Ala26Ser), gnomAD rs1403142128, REVEL 0.28, CADD 4.09
- A26V (p.Ala26Val), rs1329279009, ClinGen CA404483547, ClinVar RCV001934548, TOPMed rs1329279009, REVEL 0.30, CADD 14.30, Uncertain significance, not provided
- L27P (p.Leu27Pro), Ensembl rs2047006980, REVEL 0.65, CADD 22.70
- L27Q (p.Leu27Gln), Ensembl rs2047006980, REVEL 0.52, CADD 23.50
- L27R (p.Leu27Arg), Ensembl rs2047006980
- P28L (p.Pro28Leu), ExAC rs750802043, gnomAD rs750802043, REVEL 0.33, CADD 16.90, Uncertain significance
- P28R (p.Pro28Arg), rs750802043, ClinGen CA404483537, ClinVar RCV003837172, ExAC rs750802043, REVEL 0.43, CADD 17.70, Uncertain significance, not provided
- P28S (p.Pro28Ser), Ensembl rs2145457503, REVEL 0.32, CADD 19.30
- L30V (p.Leu30Val), gnomAD rs1478837820, REVEL 0.35, CADD 18.70
- A34V (p.Ala34Val), gnomAD rs1177819313, REVEL 0.32, CADD 21.40
- G35E (p.Gly35Glu), Ensembl rs2047006730, REVEL 0.50, CADD 23.80
- G35W (p.Gly35Trp), NCI-TCGA TCGA novel, REVEL 0.55, CADD 27.20, Variant assessed as somatic; moderate impact.
- P36L (p.Pro36Leu), rs1311684711, ClinGen CA404483494, ClinVar RCV001334447, ClinVar RCV001871861, REVEL 0.19, CADD 18.00, Uncertain significance, not provided; Cerebral arteriopathy, autosomal dominant, with subcortical infarc
- P36S (p.Pro36Ser), gnomAD rs1199131419, REVEL 0.28, CADD 17.20
- G37R (p.Gly37Arg), 1000Genomes rs757705816, ExAC rs757705816, gnomAD rs757705816, REVEL 0.46, CADD 22.00
- G37V (p.Gly37Val), TOPMed rs2047006556, REVEL 0.42, CADD 18.20
- A38G (p.Ala38Gly), Ensembl rs2145457357, REVEL 0.34, CADD 23.40
- A38S (p.Ala38Ser), rs752064930, ClinGen CA404483487, ClinVar RCV003880537, ExAC rs752064930, REVEL 0.32, CADD 21.70, Uncertain significance, not provided
- A38T (p.Ala38Thr), ExAC rs752064930, TOPMed rs752064930, gnomAD rs752064930, REVEL 0.33, CADD 22.70, Uncertain significance
- A39T (p.Ala39Thr), Ensembl rs2145457351, REVEL 0.38, CADD 21.70
- A40D (p.Ala40Asp), ExAC rs766139231, gnomAD rs766139231, REVEL 0.41, CADD 16.90, Uncertain significance
- A40G (p.Ala40Gly), ExAC rs766139231, gnomAD rs766139231, REVEL 0.35, CADD 16.60, Uncertain significance
- A40V (p.Ala40Val), rs766139231, ClinGen CA9263998, ClinVar RCV001947722, ClinVar RCV002479405, REVEL 0.39, CADD 19.40, Uncertain significance, not provided; Cerebral arteriopathy, autosomal dominant, with subcortical infarc
- P41T (p.Pro41Thr), TOPMed rs2046978928, REVEL 0.27, CADD 13.70
- P42A (p.Pro42Ala), 1000Genomes rs372995747, ESP rs372995747, ExAC rs372995747, TOPMed rs372995747, REVEL 0.26, CADD 15.10, Uncertain significance
- P42R (p.Pro42Arg), Ensembl rs2046978842, REVEL 0.35, CADD 22.30
- P42S (p.Pro42Ser), rs372995747, ClinGen CA9263995, ClinVar RCV004488237, 1000Genomes rs372995747, REVEL 0.21, CADD 16.50, Uncertain significance, Inborn genetic diseases
- P42T (p.Pro42Thr), 1000Genomes rs372995747, ESP rs372995747, ExAC rs372995747, TOPMed rs372995747, REVEL 0.24, CADD 15.80, Uncertain significance
- C43* (p.Cys43Ter), NCI-TCGA Cosmic COSV9965, Variant assessed as somatic; high impact., in CADASIL1
- C43F (p.Cys43Phe), Ensembl rs1555730204, Pathogenic, not provided
- C43G (p.Cys43Gly), UniProt VAR 044230, Likely pathogenic, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen
- C43Y (p.Cys43Tyr), rs1555730204, ClinGen CA404483448, ClinVar RCV000517549, ClinVar RCV005431723, AlphaMissense 0.72, MetaLR 1.00, Pathogenic, not provided; Cerebral arteriopathy, autosomal dominant, with subcortical infarc
- D45G (p.Asp45Gly), Ensembl rs2145451312, MetaLR 0.89, MetaSVM 0.80
- D45H (p.Asp45His), rs142031490, ClinGen CA9263992, ClinVar RCV000518589, ClinVar RCV001787100, REVEL 0.72, CADD 24.80, Uncertain significance, not specified; not provided
- D45N (p.Asp45Asn), ESP rs142031490, ExAC rs142031490, gnomAD rs142031490, REVEL 0.36, CADD 23.30, Uncertain significance
- D45V (p.Asp45Val), Ensembl rs2145451312, REVEL 0.82, CADD 27.50
- G46R (p.Gly46Arg), ExAC rs748968901, TOPMed rs748968901, gnomAD rs748968901, REVEL 0.31, CADD 23.10
- S47G (p.Ser47Gly), rs775259883, ClinGen CA9263989, ClinVar RCV001128002, ClinVar RCV002473202, REVEL 0.34, CADD 22.30, Uncertain significance, not provided; Cerebral arteriopathy, autosomal dominant, with subcortical infarc
- S47R (p.Ser47Arg), Ensembl rs1555730199
- P48L (p.Pro48Leu), rs1362111590, ClinGen CA404483413, ClinVar RCV001913650, TOPMed rs1362111590, REVEL 0.64, CADD 22.90, Uncertain significance, not provided
- P48Q (p.Pro48Gln), TOPMed rs1362111590, gnomAD rs1362111590, MetaLR 0.85, MetaSVM 0.89, Uncertain significance
- C49* (p.Cys49Ter), ExAC rs777943180, gnomAD rs777943180
- C49F (p.Cys49Phe), rs193921045, ClinGen CA174091, ClinVar RCV000149001, ClinVar RCV001657843, AlphaMissense 0.88, MetaLR 1.00, Pathogenic, not provided
- C49G (p.Cys49Gly), rs1555730197, ClinGen CA404483409, ClinVar RCV000710993, ClinVar RCV002485786, AlphaMissense 0.91, MetaLR 1.00, Pathogenic/Likely pathogenic, Lateral meningocele syndrome; Cerebral arteriopathy, autosomal dominant, with su
- C49R (p.Cys49Arg), rs1555730197, ClinGen CA404483412, NCI-TCGA Cosmic COSV9965, ClinVar RCV000518038, AlphaMissense 0.91, MetaLR 1.00, Pathogenic, not provided
- C49Y (p.Cys49Tyr), rs193921045, ClinGen CA404483407, ClinVar RCV000518559, ClinVar RCV005901138, AlphaMissense 0.88, MetaLR 1.00, Pathogenic, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen
- A50P (p.Ala50Pro), Ensembl rs2145451265
- A50V (p.Ala50Val), Ensembl rs2145451259, MetaLR 0.48, MetaSVM -0.57
- N51D (p.Asn51Asp), TOPMed rs1901039188, MetaLR 0.91, MetaSVM 0.80
- N51K (p.Asn51Lys), ExAC rs758951375, TOPMed rs758951375, gnomAD rs758951375, REVEL 0.57, CADD 25.70
- G52* (p.Gly52Ter), NCI-TCGA Cosmic COSV9965, Variant assessed as somatic; high impact.
- G52A (p.Gly52Ala), TOPMed rs1389999486, gnomAD rs1389999486, MetaLR 0.95, MetaSVM 1.03
- G52E (p.Gly52Glu), TOPMed rs1389999486, gnomAD rs1389999486, REVEL 0.84, CADD 23.90
- G52R (p.Gly52Arg), rs148166997, ClinGen CA9263984, ClinVar RCV000516491, ClinVar RCV001787102, REVEL 0.87, CADD 29.70, Uncertain significance, not specified; not provided
- G53D (p.Gly53Asp), TOPMed rs2046978438, MetaLR 0.95, MetaSVM 1.08
- G53R (p.Gly53Arg), ExAC rs778989879, TOPMed rs778989879, gnomAD rs778989879, REVEL 0.87, CADD 27.00, Uncertain significance
- G53S (p.Gly53Ser), rs778989879, ClinGen CA9263983, ClinVar RCV001769084, ExAC rs778989879, REVEL 0.83, CADD 26.50, Uncertain significance, not provided
- R54C (p.Arg54Cys), rs1555730189, ClinGen CA404483379, ClinVar RCV000516423, ClinVar RCV001253276, REVEL 0.80, CADD 32.00, Pathogenic/Likely pathogenic, Lateral meningocele syndrome; Myofibromatosis, infantile, 2; Cerebral arteriopat
- R54H (p.Arg54His), rs754104109, ClinGen CA9263981, ClinVar RCV001663831, ExAC rs754104109, REVEL 0.49, CADD 23.90, Uncertain significance, not provided
- R54L (p.Arg54Leu), ExAC rs754104109, TOPMed rs754104109, gnomAD rs754104109, REVEL 0.51, CADD 23.60, Uncertain significance, in CADASIL1
- C55R (p.Cys55Arg), rs1568363980, ClinGen CA404483376, ClinVar RCV000710994, Ensembl rs1568363980, AlphaMissense 0.91, MetaLR 1.00, Pathogenic, not provided
- C55Y (p.Cys55Tyr), rs1555730188, ClinGen CA404483372, ClinVar RCV000516615, ClinVar RCV000990180, AlphaMissense 0.86, MetaLR 1.00, Pathogenic/Likely pathogenic, not provided; Cerebral arteriopathy, autosomal dominant, with subcortical infarc
- T56I (p.Thr56Ile), Ensembl rs2145451166, MetaLR 0.79, MetaSVM 0.26
- T56P (p.Thr56Pro), Ensembl rs2145451174, REVEL 0.67, CADD 24.30
- Q57* (p.Gln57Ter), rs1555730187, ClinGen CA404483361, ClinVar RCV003326718, AlphaMissense 0.15, MetaLR 0.81, Likely pathogenic
- Q57H (p.Gln57His), rs755917588, NCI-TCGA Cosmic COSV5463, ExAC rs755917588, TOPMed rs755917588, REVEL 0.46, CADD 23.30, Likely benign, not provided
- Q57K (p.Gln57Lys), Ensembl rs1555730187
- Q57R (p.Gln57Arg), TOPMed rs2046978227, REVEL 0.50, CADD 20.90
- P59S (p.Pro59Ser), Ensembl rs2145451112, REVEL 0.36, CADD 17.60
- S60C (p.Ser60Cys), UniProt VAR 044233, Pathogenic, in CADASIL1
- S60P (p.Ser60Pro), ExAC rs750242461, gnomAD rs750242461, REVEL 0.49, CADD 23.20
- R61G (p.Arg61Gly), ESP rs200595885, ExAC rs200595885, TOPMed rs200595885, gnomAD rs200595885, REVEL 0.25, CADD 12.50, Uncertain significance, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen
- R61Q (p.Arg61Gln), rs1222763947, ClinGen CA404483339, ClinVar RCV002593159, TOPMed rs1222763947, REVEL 0.20, CADD 15.90, Uncertain significance, not provided
- R61W (p.Arg61Trp), rs200595885, ClinGen CA9263976, ClinVar RCV001859429, ClinVar RCV005412273, REVEL 0.47, CADD 23.80, Likely benign, not provided
- E62G (p.Glu62Gly), gnomAD rs1317877838, REVEL 0.61, CADD 24.90
- A63P (p.Ala63Pro), Ensembl rs864621964, Pathogenic
- A63T (p.Ala63Thr), rs864621964, ClinGen CA340886, ClinVar RCV000009802, Ensembl rs864621964, REVEL 0.25, CADD 21.60, Pathogenic, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen
- A64D (p.Ala64Asp), rs148932488, ClinGen CA9263975, ClinVar RCV002721943, ClinVar RCV004642017, REVEL 0.56, CADD 23.50, Conflicting interpretations, not specified; not provided; Inborn genetic diseases
- A64S (p.Ala64Ser), Ensembl rs2145451051, MetaLR 0.72, MetaSVM 0.43
- C65F (p.Cys65Phe), rs1555730176, ClinGen CA404483313, ClinVar RCV001248779, ClinVar RCV004727046, AlphaMissense 0.85, MetaLR 1.00, Pathogenic, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen
- C65G (p.Cys65Gly), rs1555730177, ClinGen CA404483316, ClinVar RCV000518666, Ensembl rs1555730177, AlphaMissense 0.81, MetaLR 1.00, Pathogenic, not provided
- C65S (p.Cys65Ser), rs1555730176, ClinGen CA404483314, ClinVar RCV000517084, ClinVar RCV001253000, AlphaMissense 0.85, MetaLR 1.00, Pathogenic/Likely pathogenic, Adams-Oliver syndrome 5; not provided; Cerebral arteriopathy, autosomal dominant
- C65Y (p.Cys65Tyr), rs1555730176, ClinGen CA404483315, ClinVar RCV001942733, ClinVar RCV002291003, AlphaMissense 0.85, MetaLR 1.00, Pathogenic/Likely pathogenic, not provided; Cerebral arteriopathy, autosomal dominant, with subcortical infarc
- C67F (p.Cys67Phe), rs1555729615, ClinGen CA404535226, ClinVar RCV000516950, Ensembl rs1555729615, AlphaMissense 0.98, MetaLR 1.00, Pathogenic/Likely pathogenic, not provided; Cerebral arteriopathy, autosomal dominant, with subcortical infarc
- C67G (p.Cys67Gly), Ensembl rs2145443955, Pathogenic, in CADASIL1
- C67S (p.Cys67Ser), rs2145443955, ClinGen CA404535232, ClinVar RCV002475355, Ensembl rs2145443955, AlphaMissense 0.99, MetaLR 1.00, Pathogenic, not provided
- C67Y (p.Cys67Tyr), rs1555729615, UniProt VAR 044235, Ensembl rs1555729615, AlphaMissense 0.98, MetaLR 1.00, Uncertain significance, not specified
- P68A (p.Pro68Ala), Ensembl rs919570567
- P68L (p.Pro68Leu), rs146810942, ClinGen CA9263952, ClinVar RCV000286129, ClinVar RCV000516451, REVEL 0.23, CADD 13.90, Conflicting interpretations, not specified; not provided; NOTCH3-related disorder
- P68R (p.Pro68Arg), ESP rs146810942, ExAC rs146810942, TOPMed rs146810942, gnomAD rs146810942, MetaLR 0.59, MetaSVM -0.44, Likely benign
- P68S (p.Pro68Ser), Ensembl rs919570567, REVEL 0.31, CADD 20.50
- P69A (p.Pro69Ala), Ensembl rs2145443909
- P69L (p.Pro69Leu), gnomAD rs2046938354, REVEL 0.43, CADD 21.40
- P69R (p.Pro69Arg), gnomAD rs2046938354, MetaLR 0.89, MetaSVM 1.00, Uncertain significance, Inborn genetic diseases
- P69S (p.Pro69Ser), Ensembl rs2145443909, REVEL 0.44, CADD 15.80
- G70A (p.Gly70Ala), gnomAD rs1174452738
- G70C (p.Gly70Cys), rs1379608507, ClinGen CA404535199, ClinVar RCV003721166, ClinVar RCV004539064, AlphaMissense 0.29, MetaLR 0.95, Uncertain significance, not provided
- G70D (p.Gly70Asp), gnomAD rs1174452738, REVEL 0.89, CADD 23.50
- G70S (p.Gly70Ser), gnomAD rs1379608507, REVEL 0.82, AlphaMissense 0.29
- G70V (p.Gly70Val), gnomAD rs1174452738, MetaLR 0.97, MetaSVM 1.10
- W71* (p.Trp71Ter), TOPMed rs2046938295
- W71C (p.Trp71Cys), rs28937321, ClinGen CA340883, ClinVar RCV000009799, ClinVar RCV001659689, AlphaMissense 0.95, MetaLR 0.95, Pathogenic, not provided
- W71L (p.Trp71Leu), TOPMed rs2046938295, REVEL 0.49, CADD 21.50
- W71R (p.Trp71Arg), Ensembl rs2145443875, MetaLR 0.91, MetaSVM 0.95
- V72L (p.Val72Leu), TOPMed rs2046938247, gnomAD rs2046938247, Uncertain significance
- V72M (p.Val72Met), rs2046938247, ClinGen CA404535180, ClinVar RCV001334449, ClinVar RCV004035779, REVEL 0.43, CADD 22.40, Uncertain significance, Inborn genetic diseases; Myofibromatosis, infantile, 2
- G73C (p.Gly73Cys), Ensembl rs2145443842, REVEL 0.94, CADD 26.20
- G73D (p.Gly73Asp), Ensembl rs2145443837, MetaLR 0.97, MetaSVM 1.11, Uncertain significance
- G73V (p.Gly73Val), rs2145443837, ClinGen CA404535164, ClinVar RCV002475333, Ensembl rs2145443837, REVEL 0.96, CADD 24.50, Uncertain significance, not provided
- E74* (p.Glu74Ter), TOPMed rs1439473554, gnomAD rs1439473554
- E74G (p.Glu74Gly), Ensembl rs2145443825
- E74K (p.Glu74Lys), TOPMed rs1439473554, gnomAD rs1439473554
- E74V (p.Glu74Val), Ensembl rs2145443825, MetaLR 0.68, MetaSVM -0.05
- R75G (p.Arg75Gly), ExAC rs762164861, TOPMed rs762164861, gnomAD rs762164861, Benign
- R75L (p.Arg75Leu), 1000Genomes rs145069047, ESP rs145069047, ExAC rs145069047, TOPMed rs145069047, REVEL 0.37, CADD 11.90, Pathogenic
- R75P (p.Arg75Pro), rs145069047, ClinGen CA404535148, ClinVar RCV000779253, ClinVar RCV002473131, REVEL 0.68, CADD 20.90, Pathogenic/Likely pathogenic, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen
- R75Q (p.Arg75Gln), rs145069047, ClinGen CA9263949, ClinVar RCV000945357, ClinVar RCV001374641, REVEL 0.42, CADD 19.40, Conflicting interpretations, not provided; Cerebral arteriopathy, autosomal dominant, with subcortical infarc
- R75W (p.Arg75Trp), rs762164861, ClinGen CA9263950, ClinVar RCV001663841, ClinVar RCV001859430, REVEL 0.49, CADD 14.90, Benign/Likely benign, not provided; not specified
- C76* (p.Cys76Ter), Ensembl rs2145443753, Uncertain significance, in CADASIL1
- C76F (p.Cys76Phe), Ensembl rs1568362252, Pathogenic, in CADASIL1
- C76G (p.Cys76Gly), Ensembl rs1555729610, Pathogenic, in CADASIL1
- C76R (p.Cys76Arg), rs1555729610, ClinGen CA404535145, ClinVar RCV000518298, UniProt VAR 044236, AlphaMissense 1.00, MetaLR 1.00, Pathogenic, not provided
- C76S (p.Cys76Ser), rs1555729610, ClinGen CA404535146, ClinVar RCV000710996, Ensembl rs1555729610, AlphaMissense 1.00, MetaLR 1.00, Pathogenic, not provided
- C76W (p.Cys76Trp), rs2145443753, UniProt VAR 044237, Ensembl rs2145443753, AlphaMissense 0.99, MetaLR 0.99, Uncertain significance, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen
- C76Y (p.Cys76Tyr), rs1568362252, ClinGen CA404535141, ClinVar RCV000710997, ClinVar RCV001003549, AlphaMissense 1.00, MetaLR 1.00, Pathogenic, not provided
- Q77* (p.Gln77Ter), Ensembl rs2145443742
- Q77E (p.Gln77Glu), Ensembl rs2145443742
- Q77H (p.Gln77His), rs1438944422, gnomAD rs1438944422, ClinGen CA404535126, ClinVar RCV001663843, REVEL 0.67, CADD 18.80, Uncertain significance, not provided
- Q77L (p.Gln77Leu), Ensembl rs2145443733, MetaLR 0.95, MetaSVM 1.08
- L78Q (p.Leu78Gln), Ensembl rs2145443706
- L78V (p.Leu78Val), gnomAD rs2046938023
- E79D (p.Glu79Asp), Ensembl rs2145443680
- E79G (p.Glu79Gly), NCI-TCGA TCGA novel, Ensembl rs2145443689, Variant assessed as somatic; moderate impact.
- E79Q (p.Glu79Gln), TOPMed rs969513308, REVEL 0.34, CADD 16.30
- E79V (p.Glu79Val), Ensembl rs2145443689
- D80A (p.Asp80Ala), Ensembl rs1599395616, REVEL 0.85, AlphaMissense 0.97, Likely pathogenic
- D80E (p.Asp80Glu), gnomAD rs1256046042, REVEL 0.58, CADD 22.10
- D80G (p.Asp80Gly), rs1599395616, ClinGen CA404535099, ClinVar RCV001812344, ClinVar RCV004796409, AlphaMissense 0.97, MetaLR 0.93, Conflicting interpretations, not provided; Cerebral arteriopathy, autosomal dominant, with subcortical infarc
- D80N (p.Asp80Asn), gnomAD rs2046937977
- D80V (p.Asp80Val), Ensembl rs1599395616, MetaLR 0.96, MetaSVM 1.09, Likely pathogenic
- P81H (p.Pro81His), ExAC rs749724379, gnomAD rs749724379, REVEL 0.75, CADD 25.90
- P81L (p.Pro81Leu), ExAC rs749724379, gnomAD rs749724379, REVEL 0.69, CADD 25.90
- P81R (p.Pro81Arg), ExAC rs749724379, gnomAD rs749724379, MetaLR 0.95, MetaSVM 1.09
- P81S (p.Pro81Ser), ExAC rs769161256, gnomAD rs769161256, REVEL 0.65, CADD 23.30
- P81T (p.Pro81Thr), ExAC rs769161256, gnomAD rs769161256, REVEL 0.65, CADD 21.80
- C82F (p.Cys82Phe), rs1023306013, ClinGen CA305778444, ClinVar RCV000516733, ClinVar RCV004737588, AlphaMissense 0.99, MetaLR 0.99, Pathogenic/Likely pathogenic, Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoen
- C82G (p.Cys82Gly), rs2046937845, ClinGen CA404535083, ClinVar RCV001288886, ClinVar RCV005057214, AlphaMissense 0.98, MetaLR 0.99, Conflicting interpretations, not specified; not provided
- C82R (p.Cys82Arg), rs2046937845, ClinGen CA404535085, ClinVar RCV001663844, ClinVar RCV004738356, AlphaMissense 0.98, MetaLR 0.99, Pathogenic, not provided
- C82S (p.Cys82Ser), TOPMed rs1023306013, Pathogenic
- C82W (p.Cys82Trp), Ensembl rs2145443604, MetaLR 0.99, MetaSVM 0.94
Public NOTCH3 analysis runs
- NOTCH3 analysis run — NOTCH3 (5,573 variants) — completed 2026-08-18