NCSTN (Nicastrin) variants and mutations
NCSTN (also known as Nicastrin) is a human protein-coding gene encoding a nicastrin protein. An essential subunit of the gamma-secretase complex, an intramembrane protease that processes proteins such as Notch receptors and APP. Through this complex it contributes to cell-signaling pathways and has relevance to skin disease and amyloid biology. This analysis covers 905 NCSTN variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes acne inversa, familial, 1, neurodegenerative disease, and Desmoid-type fibromatosis. Example NCSTN variants include A2T, A2V, and T3M.
Variant analysis overview
- Gene: NCSTN
- Protein: Nicastrin
- UniProt accession: Q92542
- Organism: Homo sapiens
- Variants analyzed: 905
- Variant scope: all variants
- Completed: 2026-06-01
Variant and mutation evidence
- Variant composition: 729 unspecified-consequence records; 102 missense variants; 53 synonymous variants; 8 frameshift variants; 2 in-frame deletions; 4 stop-gained variants; 3 splice-region variants; 4 substitution
- Prediction scores: 883 variants have prediction scores (98% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: acne inversa, familial, 1, neurodegenerative disease, Desmoid-type fibromatosis, neoplasm, Alzheimer disease, hidradenitis suppurativa, Pyoderma gangrenosum-acne-suppurative hidradenitis syndrome, Abnormality of the skin, Parkinson disease, Follicular Cyst, skin disease, skin appendage disorder.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 16 post-translational modification sites.
- Structural context: 19 variants have structural context.
- PTM context: 22 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, PharmGKB, MaveDB, LitVar.
Notable NCSTN variants
Examples include A2T, A2V, T3M, T3A, T3T, A4T, G5A, G5E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2T (p.Ala2Thr), gnomAD 1-160343400-G-A, REVEL 0.29, ESM-1b 0.00
- A2V (p.Ala2Val), gnomAD 1-160343401-C-T, REVEL 0.25, ESM-1b 0.00
- T3M (p.Thr3Met), gnomAD rs1435524419, REVEL 0.32, ESM-1b 0.00
- T3A (p.Thr3Ala), gnomAD 1-160343403-A-G, REVEL 0.26, ESM-1b 0.00
- T3T (p.Thr3Thr), rs201357529, gnomAD 1-160343405-G-A, CADD 5.02
- A4T (p.Ala4Thr), gnomAD 1-160343406-G-A, REVEL 0.11, ESM-1b 0.00
- G5A (p.Gly5Ala), 1000Genomes rs528352370, ExAC rs528352370, TOPMed rs528352370, gnomAD rs528352370, REVEL 0.15, ESM-1b 0.00, Uncertain significance
- G5E (p.Gly5Glu), rs528352370, ClinGen CA1198538, ClinVar RCV001927588, 1000Genomes rs528352370, REVEL 0.12, ESM-1b 0.00, Uncertain significance, not provided
- G5V (p.Gly5Val), rs528352370, ClinGen CA1198537, ClinVar RCV003725404, 1000Genomes rs528352370, REVEL 0.12, ESM-1b 0.00, Uncertain significance, not provided
- G5G (p.Gly5Gly), gnomAD 1-160343411-G-C, CADD 9.31
- G6A (p.Gly6Ala), TOPMed rs1243549103, gnomAD rs1243549103, REVEL 0.17, ESM-1b 0.00
- G6V (p.Gly6Val), TOPMed rs1243549103, gnomAD rs1243549103, REVEL 0.31, ESM-1b 0.00, Uncertain significance, not provided
- G6G (p.Gly6Gly), rs201989234, gnomAD 1-160343414-T-G, CADD 13.60
- G7C (p.Gly7Cys), ExAC rs773067948, gnomAD rs773067948, REVEL 0.24, ESM-1b 0.00
- G7D (p.Gly7Asp), NCI-TCGA TCGA novel, REVEL 0.26, ESM-1b 0.09, Variant assessed as somatic; moderate impact.
- G7W (p.Gly7Trp), rs1266104510, gnomAD 1-160343408-A-AG, CADD 23.50
- p.Gly7 Ala10del, gnomAD 1-160343413-GTGGC, CADD 16.10
- G7R (p.Gly7Arg), gnomAD 1-160343415-G-C, REVEL 0.23, ESM-1b 0.00
- G7G (p.Gly7Gly), rs1415017171, gnomAD 1-160343417-C-T, CADD 12.70
- S8C (p.Ser8Cys), ExAC rs770476356, gnomAD rs770476356, REVEL 0.19, ESM-1b 0.00, Uncertain significance
- S8F (p.Ser8Phe), rs770476356, ClinGen CA343274356, NCI-TCGA Cosmic COSV9961, ClinVar RCV001946364, ESM-1b 0.00, AlphaMissense 0.08, Uncertain significance, not provided
- S8P (p.Ser8Pro), ExAC rs749209748, gnomAD rs749209748, REVEL 0.24, ESM-1b 0.00
- S8A (p.Ser8Ala), gnomAD 1-160343418-T-G, REVEL 0.14, ESM-1b 0.00
- G9A (p.Gly9Ala), rs1041921165, ClinGen CA31530008, ClinVar RCV003565960, TOPMed rs1041921165, ESM-1b 0.00, AlphaMissense 0.06, Uncertain significance, not provided
- G9E (p.Gly9Glu), rs1041921165, ClinGen CA343274365, ClinVar RCV002994031, TOPMed rs1041921165, REVEL 0.29, ESM-1b 0.00, Uncertain significance, not provided
- G9V (p.Gly9Val), TOPMed rs1041921165, REVEL 0.27, ESM-1b 0.00, Uncertain significance, not provided
- G9G (p.Gly9Gly), rs1557880042, gnomAD 1-160343423-G-C, CADD 8.93
- A10G (p.Ala10Gly), Ensembl rs2101885953, REVEL 0.14, ESM-1b 0.00
- A10T (p.Ala10Thr), TOPMed rs1648210105, gnomAD rs1648210105, REVEL 0.21, ESM-1b 0.00
- A10P (p.Ala10Pro), gnomAD 1-160343424-G-C, REVEL 0.31, ESM-1b 0.00
- A10A (p.Ala10Ala), rs1388458406, gnomAD 1-160343426-T-G, CADD 8.21
- D11H (p.Asp11His), TOPMed rs1648210558, REVEL 0.27, ESM-1b 0.00, Uncertain significance, Inborn genetic diseases
- D11N (p.Asp11Asn), NCI-TCGA Cosmic COSV5409, TOPMed rs1648210558, REVEL 0.17, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- D11Y (p.Asp11Tyr), gnomAD 1-160343715-G-T, REVEL 0.09, CADD 12.40
- D11* (p.Asp11Ter), gnomAD 1-160343725-C-CT, CADD 7.41
- D11D (p.Asp11Asp), gnomAD 1-160343729-C-T, CADD 10.60
- P12A (p.Pro12Ala), Ensembl rs1648210869, REVEL 0.17, ESM-1b 0.00
- P12L (p.Pro12Leu), ExAC rs773818422, gnomAD rs773818422, REVEL 0.19, ESM-1b 0.00
- P12R (p.Pro12Arg), ExAC rs773818422, gnomAD rs773818422, REVEL 0.22, ESM-1b 0.00
- P12S (p.Pro12Ser), gnomAD 1-160343430-C-T, REVEL 0.15, ESM-1b 0.00
- P12Q (p.Pro12Gln), gnomAD 1-160343431-C-A, REVEL 0.17, ESM-1b 0.00
- G13E (p.Gly13Glu), gnomAD 1-160343434-G-A, REVEL 0.37, ESM-1b 0.00
- G13A (p.Gly13Ala), gnomAD 1-160343434-G-C, REVEL 0.19, ESM-1b 0.00
- S14G (p.Ser14Gly), rs1362905608, ClinGen CA343274413, ClinVar RCV003837143, TOPMed rs1362905608, REVEL 0.17, ESM-1b 0.00, Uncertain significance, not provided
- S14S (p.Ser14Ser), rs759140355, gnomAD 1-160343438-T-C, CADD 15.40
- R15P (p.Arg15Pro), ExAC rs767145960, TOPMed rs767145960, gnomAD rs767145960, REVEL 0.35, ESM-1b 0.00
- R15W (p.Arg15Trp), gnomAD 1-160343439-C-T, REVEL 0.27, ESM-1b 0.00
- R15Q (p.Arg15Gln), gnomAD 1-160343440-G-A, REVEL 0.15, ESM-1b 0.00
- R15R (p.Arg15Arg), rs776870343, gnomAD 1-160343441-G-C, CADD 13.60
- G16D (p.Gly16Asp), Ensembl rs767169419, REVEL 0.31, ESM-1b 0.00
- L17V (p.Leu17Val), rs200632380, ClinGen CA1198548, ClinVar RCV001953359, ExAC rs200632380, REVEL 0.08, ESM-1b 0.00, Uncertain significance, not provided
- L17L (p.Leu17Leu), rs1315207209, gnomAD 1-160343447-C-T, CADD 10.90
- L18F (p.Leu18Phe), ESP rs376983649, TOPMed rs376983649, gnomAD rs376983649, REVEL 0.15, ESM-1b 0.19, Uncertain significance
- L18V (p.Leu18Val), rs376983649, ClinGen CA343274442, ClinVar RCV003734945, ESP rs376983649, REVEL 0.25, ESM-1b 0.00, Uncertain significance, not provided
- L18S (p.Leu18Ser), gnomAD 1-160343443-G-GTC, CADD 24.70
- L18del (p.Leu18del), rs764980428, gnomAD 1-160343447-CCTT-, CADD 20.60
- L18P (p.Leu18Pro), gnomAD 1-160343449-T-C, REVEL 0.50, ESM-1b 0.00
- L18L (p.Leu18Leu), rs141165822, gnomAD 1-160343450-T-G, CADD 11.50
- R19C (p.Arg19Cys), rs751031803, ClinGen CA1198551, ClinVar RCV003726532, ExAC rs751031803, REVEL 0.36, ESM-1b 0.00, Uncertain significance, not provided
- R19G (p.Arg19Gly), ExAC rs751031803, TOPMed rs751031803, gnomAD rs751031803, REVEL 0.34, ESM-1b 0.00, Uncertain significance
- R19H (p.Arg19His), rs201530191, ClinGen CA1198552, ClinVar RCV003092647, ClinVar RCV005399101, REVEL 0.22, ESM-1b 0.00, Uncertain significance, Inborn genetic diseases; not provided; Acne inversa, familial, 1
- L20F (p.Leu20Phe), TOPMed rs1285710472, gnomAD rs1285710472, REVEL 0.16, ESM-1b 0.00
- L20V (p.Leu20Val), rs1285710472, NCI-TCGA Cosmic COSV5411, TOPMed rs1285710472, gnomAD rs1285710472, REVEL 0.16, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- L20L (p.Leu20Leu), gnomAD 1-160343456-T-C, CADD 12.50
- L21M (p.Leu21Met), ExAC rs199694056, TOPMed rs199694056, gnomAD rs199694056, REVEL 0.37, ESM-1b 1.00, Likely benign
- L21P (p.Leu21Pro), rs2525487202, ClinGen CA343274460, ClinVar RCV002856602, REVEL 0.61, ESM-1b 1.00, Uncertain significance, not provided
- L21V (p.Leu21Val), ExAC rs199694056, TOPMed rs199694056, gnomAD rs199694056, REVEL 0.12, ESM-1b 0.00, Likely benign
- L21L (p.Leu21Leu), rs199694056, gnomAD 1-160343457-C-T, CADD 12.80
- S22P (p.Ser22Pro), TOPMed rs1648216449, REVEL 0.33, ESM-1b 0.00
- S22F (p.Ser22Phe), gnomAD 1-160343461-C-T, REVEL 0.32, ESM-1b 0.00
- S22Y (p.Ser22Tyr), gnomAD 1-160343461-C-A, REVEL 0.27, ESM-1b 0.00
- F23C (p.Phe23Cys), gnomAD rs1648216643, REVEL 0.35, ESM-1b 0.00
- F23V (p.Phe23Val), gnomAD 1-160343709-T-G, REVEL 0.02, CADD 8.58
- F23L (p.Phe23Leu), gnomAD 1-160343711-C-A, REVEL 0.02, CADD 5.15
- F23S (p.Phe23Ser), gnomAD 1-160343756-GT-G, CADD 7.38
- F23I (p.Phe23Ile), gnomAD 1-160343760-T-A, REVEL 0.02, CADD 8.40
- F23F (p.Phe23Phe), gnomAD 1-160343762-C-T, CADD 6.22
- C24Y (p.Cys24Tyr), 1000Genomes rs530941300, ExAC rs530941300, TOPMed rs530941300, gnomAD rs530941300, REVEL 0.27, ESM-1b 0.10
- C24S (p.Cys24Ser), gnomAD 1-160343467-G-C, REVEL 0.24, ESM-1b 0.00
- C24C (p.Cys24Cys), gnomAD 1-160343468-C-T, CADD 16.70
- V25I (p.Val25Ile), rs1237630488, ClinGen CA343274482, ClinVar RCV001924403, ClinVar RCV005684831, REVEL 0.04, ESM-1b 0.00, Uncertain significance, Inborn genetic diseases; not provided
- V25F (p.Val25Phe), gnomAD 1-160343469-G-T, REVEL 0.28, ESM-1b 0.00
- V25A (p.Val25Ala), gnomAD 1-160343470-T-C, REVEL 0.19, ESM-1b 0.00
- V25V (p.Val25Val), gnomAD 1-160343471-C-A, CADD 12.90
- L26R (p.Leu26Arg), ExAC rs781420066, REVEL 0.47, ESM-1b 1.00
- L26L (p.Leu26Leu), rs1401602646, gnomAD 1-160343474-A-G, CADD 5.93
- L27L (p.Leu27Leu), rs1362324068, gnomAD 1-160343475-C-T, CADD 15.40
- L27I (p.Leu27Ile), gnomAD 1-160343475-C-A, REVEL 0.20, ESM-1b 0.55
- A28T (p.Ala28Thr), rs1648227637, ClinGen CA343274497, ClinVar RCV003009512, Ensembl rs1648227637, REVEL 0.10, ESM-1b 0.00, Uncertain significance, not provided
- A28S (p.Ala28Ser), gnomAD 1-160343478-G-T, REVEL 0.17, ESM-1b 0.00
- A28E (p.Ala28Glu), gnomAD 1-160343479-C-A, REVEL 0.33, ESM-1b 1.00
- A28V (p.Ala28Val), gnomAD 1-160343479-C-T, REVEL 0.20, ESM-1b 0.00
- G29D (p.Gly29Asp), rs920000413, ClinGen CA343275135, ClinVar RCV001944727, gnomAD rs920000413, ESM-1b 0.08, AlphaMissense 0.22, Uncertain significance, not provided
- G29V (p.Gly29Val), rs920000413, ClinGen CA31530932, ClinVar RCV002594692, gnomAD rs920000413, REVEL 0.34, ESM-1b 0.00, Uncertain significance, not provided
- G29C (p.Gly29Cys), gnomAD 1-160343481-G-T, REVEL 0.53, ESM-1b 0.03
- G29G (p.Gly29Gly), rs757105967, gnomAD 1-160344723-T-C, CADD 16.40
- L30I (p.Leu30Ile), gnomAD 1-160343706-C-A, REVEL 0.10, ESM-1b 0.00
- L30V (p.Leu30Val), gnomAD 1-160343706-C-G, REVEL 0.10, ESM-1b 0.00
- L30H (p.Leu30His), rs1648256475, gnomAD 1-160343707-T-A, REVEL 0.49, ESM-1b 0.36
- L30L (p.Leu30Leu), rs906188312, gnomAD 1-160343708-C-T, CADD 7.38
- L30M (p.Leu30Met), gnomAD 1-160343712-C-A, REVEL 0.05, CADD 8.28
- L30Q (p.Leu30Gln), gnomAD 1-160343713-T-A, REVEL 0.05, CADD 5.12
- C31F (p.Cys31Phe), 1000Genomes rs539226938, ExAC rs539226938, TOPMed rs539226938, gnomAD rs539226938, REVEL 0.48, ESM-1b 1.00
- C31Y (p.Cys31Tyr), 1000Genomes rs539226938, ExAC rs539226938, TOPMed rs539226938, gnomAD rs539226938, REVEL 0.51, ESM-1b 1.00, Uncertain significance, not provided
- C31G (p.Cys31Gly), gnomAD 1-160344727-T-G, REVEL 0.52, ESM-1b 0.00
- R32K (p.Arg32Lys), TOPMed rs1205203955, gnomAD rs1205203955, REVEL 0.10, ESM-1b 0.34, Uncertain significance
- R32M (p.Arg32Met), rs1205203955, ClinGen CA343275173, ClinVar RCV001908428, TOPMed rs1205203955, ESM-1b 1.00, AlphaMissense 0.14, Uncertain significance, not provided
- R32S (p.Arg32Ser), NCI-TCGA Cosmic COSV5410, REVEL 0.25, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- R32R (p.Arg32Arg), rs1327797915, gnomAD 1-160344732-G-A, CADD 9.42
- G33R (p.Gly33Arg), rs2101889658, ClinGen CA343275176, ClinVar RCV001535813, Ensembl rs2101889658, ESM-1b 1.00, AlphaMissense 0.65, Pathogenic, Acne inversa, familial, 1
- G33V (p.Gly33Val), rs201482602, ClinGen CA1198601, ClinVar RCV002756440, ExAC rs201482602, REVEL 0.46, ESM-1b 0.06, Uncertain significance, not provided
- N34K (p.Asn34Lys), rs758241361, ClinGen CA1198602, ClinVar RCV001885548, ClinVar RCV002545763, REVEL 0.36, ESM-1b 0.00, Uncertain significance, Inborn genetic diseases; not provided
- S35W (p.Ser35Trp), gnomAD 1-160343755-C-G, REVEL 0.05, CADD 1.90
- S35* (p.Ser35Ter), gnomAD 1-160343755-C-A, CADD 1.76
- S35S (p.Ser35Ser), gnomAD 1-160343756-G-T, CADD 1.18
- V36L (p.Val36Leu), NCI-TCGA TCGA novel, REVEL 0.37, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- V36V (p.Val36Val), rs199910329, gnomAD 1-160344744-G-A, CADD 13.50
- E37K (p.Glu37Lys), rs1288425759, gnomAD 1-160343721-G-A, REVEL 0.01, CADD 7.60
- E37E (p.Glu37Glu), rs1024367892, gnomAD 1-160343723-G-A, CADD 6.94
- R38G (p.Arg38Gly), rs137960789, ClinGen CA1198604, ClinVar RCV001957046, ESP rs137960789, REVEL 0.37, ESM-1b 0.00, Uncertain significance, not provided
- R38K (p.Arg38Lys), ExAC rs754692403, gnomAD rs754692403, REVEL 0.10, ESM-1b 0.00
- I40L (p.Ile40Leu), gnomAD rs1481562762, REVEL 0.50, ESM-1b 0.00, Uncertain significance, Inborn genetic diseases
- I40T (p.Ile40Thr), ExAC rs780927157, REVEL 0.83, ESM-1b 1.00
- Y41H (p.Tyr41His), gnomAD rs1207593754, REVEL 0.89, ESM-1b 1.00, Uncertain significance, Inborn genetic diseases
- Y41Y (p.Tyr41Tyr), rs747798872, gnomAD 1-160344759-T-C, CADD 11.10
- I42V (p.Ile42Val), rs200640464, ClinGen CA1198608, ClinVar RCV001910228, ExAC rs200640464, REVEL 0.07, ESM-1b 0.00, Uncertain significance, not provided
- I42F (p.Ile42Phe), gnomAD 1-160344760-A-T, REVEL 0.36, ESM-1b 0.64
- I42I (p.Ile42Ile), gnomAD 1-160344762-C-T, CADD 9.69
- P43H (p.Pro43His), ExAC rs762493645, TOPMed rs762493645, gnomAD rs762493645, REVEL 0.28, ESM-1b 1.00, Uncertain significance
- P43L (p.Pro43Leu), rs762493645, ClinGen CA1198609, ClinVar RCV003728175, ExAC rs762493645, REVEL 0.29, ESM-1b 0.25, Uncertain significance, not provided
- P43R (p.Pro43Arg), ExAC rs762493645, TOPMed rs762493645, gnomAD rs762493645, REVEL 0.23, ESM-1b 1.00, Uncertain significance
- P43T (p.Pro43Thr), gnomAD 1-160343724-C-A, REVEL 0.05, CADD 6.86
- P43S (p.Pro43Ser), rs1648257894, gnomAD 1-160343724-C-T, REVEL 0.05, CADD 7.45
- P43P (p.Pro43Pro), rs886949771, gnomAD 1-160343726-T-C, CADD 6.86
- P43Q (p.Pro43Gln), gnomAD 1-160343737-C-A, REVEL 0.02, CADD 6.73
- L44I (p.Leu44Ile), ExAC rs772407803, TOPMed rs772407803, REVEL 0.34, ESM-1b 0.00
- L44F (p.Leu44Phe), gnomAD 1-160343733-C-T, REVEL 0.03, CADD 5.21
- L44L (p.Leu44Leu), gnomAD 1-160343735-C-A, CADD 4.58
- L44P (p.Leu44Pro), gnomAD 1-160343740-T-C, REVEL 0.06, CADD 12.10
- N45H (p.Asn45His), Ensembl rs891067219, ESM-1b 1.00, AlphaMissense 0.15
- N45I (p.Asn45Ile), Ensembl rs868237355, REVEL 0.63, ESM-1b 1.00
- K46E (p.Lys46Glu), gnomAD 1-160344772-A-G, REVEL 0.20, ESM-1b 0.00
- T47I (p.Thr47Ile), TOPMed rs902411403, gnomAD rs902411403, REVEL 0.50, ESM-1b 1.00
- A48D (p.Ala48Asp), NCI-TCGA TCGA novel, ESM-1b 1.00, AlphaMissense 0.84, Variant assessed as somatic; moderate impact.
- A48S (p.Ala48Ser), rs775651944, ClinGen CA343275272, ClinVar RCV002598358, ClinVar RCV004065684, REVEL 0.14, ESM-1b 0.02, Uncertain significance, Inborn genetic diseases; not provided
- A48T (p.Ala48Thr), rs775651944, NCI-TCGA Cosmic COSV9961, ExAC rs775651944, TOPMed rs775651944, REVEL 0.32, ESM-1b 1.00, Uncertain significance
- A48V (p.Ala48Val), TOPMed rs1648366091, REVEL 0.12, ESM-1b 0.85
- P49S (p.Pro49Ser), rs1648366525, ClinGen CA343275284, ClinVar RCV001974201, TOPMed rs1648366525, REVEL 0.60, ESM-1b 0.71, Uncertain significance, not provided
- P49A (p.Pro49Ala), rs1188177088, gnomAD 1-160343763-C-G, REVEL 0.01, ESM-1b 0.00
- P49R (p.Pro49Arg), rs773684044, gnomAD 1-160343764-C-G, REVEL 0.02, ESM-1b 1.00
- P49L (p.Pro49Leu), rs773684044, gnomAD 1-160343764-C-T, REVEL 0.01, ESM-1b 1.00
- P49Q (p.Pro49Gln), gnomAD 1-160343764-C-A, REVEL 0.02, ESM-1b 1.00
- P49H (p.Pro49His), gnomAD 1-160343770-C-A, REVEL 0.05, CADD 8.13
- P49V (p.Pro49Val), gnomAD 1-160343777-ACCCA, CADD 8.81
- P49P (p.Pro49Pro), gnomAD 1-160343780-C-A, CADD 7.32
- P49T (p.Pro49Thr), gnomAD 1-160343784-C-A, REVEL 0.03, CADD 7.45
- C50Y (p.Cys50Tyr), NCI-TCGA Cosmic COSV5410, REVEL 0.94, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- C50S (p.Cys50Ser), gnomAD 1-160343742-T-A, REVEL 0.05, CADD 6.08
- C50G (p.Cys50Gly), gnomAD 1-160343742-T-G, REVEL 0.07, CADD 6.26
- C50W (p.Cys50Trp), rs1648258865, gnomAD 1-160343744-T-G, REVEL 0.03, CADD 12.90
- V51I (p.Val51Ile), rs1648259771, gnomAD 1-160343751-G-A, REVEL 0.01, CADD 7.35
- V51V (p.Val51Val), rs1490781441, gnomAD 1-160343753-C-G, CADD 8.33
- R52C (p.Arg52Cys), TOPMed rs1648366732, gnomAD rs1648366732, REVEL 0.86, ESM-1b 1.00, Uncertain significance, not provided
- R52H (p.Arg52His), NCI-TCGA Cosmic COSV9961, REVEL 0.83, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- R52P (p.Arg52Pro), Ensembl rs1557881394, REVEL 0.82, ESM-1b 1.00
- R52L (p.Arg52Leu), gnomAD 1-160344791-G-T, REVEL 0.79, ESM-1b 1.00
- R52R (p.Arg52Arg), rs760678242, gnomAD 1-160344792-C-T, CADD 7.37
- L53L (p.Leu53Leu), rs145955020, gnomAD 1-160344795-G-A, CADD 10.70
- N55N (p.Asn55Asn), rs200064315, gnomAD 1-160344801-C-T, CADD 6.52
- A56T (p.Ala56Thr), rs1325765596, ClinGen CA343275359, ClinVar RCV003011380, gnomAD rs1325765596, REVEL 0.45, ESM-1b 1.00, Uncertain significance, not provided
- T57A (p.Thr57Ala), Ensembl rs1648368576, REVEL 0.80, ESM-1b 1.00
- T57I (p.Thr57Ile), ExAC rs761996747, gnomAD rs761996747, REVEL 0.73, ESM-1b 1.00
- T57S (p.Thr57Ser), NCI-TCGA Cosmic COSV5410, REVEL 0.50, ESM-1b 0.08, Variant assessed as somatic; moderate impact.
- T57P (p.Thr57Pro), gnomAD 1-160343777-AC-A, CADD 8.77
- T57T (p.Thr57Thr), gnomAD 1-160343801-A-C, CADD 18.70
- H58D (p.His58Asp), ExAC rs765124362, gnomAD rs765124362, REVEL 0.66, ESM-1b 1.00
- H58R (p.His58Arg), rs750149185, ClinGen CA1198618, ClinVar RCV002049119, ExAC rs750149185, REVEL 0.76, ESM-1b 1.00, Uncertain significance, not provided
- Q59H (p.Gln59His), rs1364710518, ClinGen CA343275394, ClinVar RCV003701360, gnomAD rs1364710518, REVEL 0.64, ESM-1b 1.00, Uncertain significance, not provided
- Q59P (p.Gln59Pro), gnomAD 1-160343767-A-C, REVEL 0.03, CADD 9.49
- Q59Q (p.Gln59Gln), rs764437174, gnomAD 1-160343768-A-G, CADD 9.55
Public NCSTN analysis runs
- NCSTN analysis run — NCSTN (905 variants) — completed 2026-06-01