NPC1 (O15118) variants and mutations
NPC1 (also known as O15118) is a human protein-coding gene encoding a NPC intracellular cholesterol transporter 1 protein. It moves cholesterol and other lipids out of late endosomes and lysosomes so they can be redistributed throughout the cell. Biallelic loss-of-function variants cause Niemann-Pick disease type C with progressive neurologic and visceral lipid-storage disease. This analysis covers 1,771 NPC1 variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes Niemann-Pick disease, type C1, Niemann-Pick disease type C, and Niemann-Pick disease. Example NPC1 variants include M1I, M1V, and T2I.
Variant analysis overview
- Gene: NPC1
- Protein: O15118
- UniProt accession: O15118
- Organism: Homo sapiens
- Variants analyzed: 1771
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,653 unspecified-consequence records; 7 stop lost; 60 missense variants; 8 frameshift variants; 28 synonymous variants; 7 stop-gained variants; 2 stop retained variant; 3 splice-region variants; 1 in-frame deletions; 2 substitution
- Prediction scores: 1,407 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Niemann-Pick disease, type C1, Niemann-Pick disease type C, Niemann-Pick disease, hereditary disease, hypertensive disorder, Abnormality of the skeletal system, obesity disorder, cerebellar ataxia, Cognitive impairment, heart failure, type 2 diabetes mellitus, Cataplexy.
Protein structure and variant hotspots
- Protein features: 13 transmembrane segments; 1 domains; 2 binding sites; 19 post-translational modification sites.
- Structural context: 417 variants have structural context.
- PTM context: 25 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 NPC1 variants
Examples include M1I, M1V, T2I, T2A, A3T, A3V, R4C, R4H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1555645630, ClinGen CA402041566, ClinVar RCV000666536, MetaLR 0.61, MetaSVM -0.08, Pathogenic/Likely pathogenic, Niemann-Pick disease, type C1
- M1V (p.Met1Val), rs1057517005, ClinGen CA16041926, ClinVar RCV000412029, MetaLR 0.61, MetaSVM -0.07, Likely pathogenic, Niemann-Pick disease, type C1
- T2I (p.Thr2Ile), TOPMed rs1390525954, gnomAD rs1390525954, REVEL 0.25, CADD 6.04
- T2A (p.Thr2Ala), rs771501685, gnomAD 18-23529695-T-C, REVEL 0.14, CADD 23.00
- A3T (p.Ala3Thr), rs752896980, ClinGen CA8913845, ClinVar RCV000671931, ClinVar RCV000728695, REVEL 0.54, CADD 17.10, Uncertain significance, not provided; Niemann-Pick disease, type C1
- A3V (p.Ala3Val), rs1321449179, ClinGen CA402041553, ClinVar RCV003056321, TOPMed rs1321449179, REVEL 0.35, CADD 14.50, Uncertain significance, Niemann-Pick disease, type C1
- R4C (p.Arg4Cys), TOPMed rs1022742391, gnomAD rs1022742391, REVEL 0.23, CADD 19.00
- R4H (p.Arg4His), Ensembl rs2059418709, REVEL 0.26, CADD 13.70
- G5D (p.Gly5Asp), Ensembl rs866847441, REVEL 0.21, CADD 14.20
- G5S (p.Gly5Ser), TOPMed rs1217477927, gnomAD rs1217477927, REVEL 0.11, CADD 14.80
- L8F (p.Leu8Phe), gnomAD rs1218989039, REVEL 0.30, CADD 14.20
- L8P (p.Leu8Pro), TOPMed rs1012718245, Uncertain significance
- L8R (p.Leu8Arg), rs1012718245, ClinGen CA297085317, ClinVar RCV001898359, ClinVar RCV003228015, AlphaMissense 0.11, MetaLR 0.70, Uncertain significance, Niemann-Pick disease, type C1; not provided
- G9S (p.Gly9Ser), rs1365975754, ClinGen CA402041526, ClinVar RCV002738319, TOPMed rs1365975754, REVEL 0.29, CADD 2.63, Uncertain significance, Inborn genetic diseases
- L10F (p.Leu10Phe), rs1272422974, ClinGen CA402041518, ClinVar RCV002002982, gnomAD rs1272422974, REVEL 0.37, CADD 14.90, Uncertain significance, Niemann-Pick disease, type C1
- L11F (p.Leu11Phe), TOPMed rs1364471701, gnomAD rs1364471701, REVEL 0.37, CADD 21.40, Uncertain significance
- L11V (p.Leu11Val), rs1364471701, ClinGen CA402041514, ClinVar RCV003058866, TOPMed rs1364471701, REVEL 0.30, CADD 19.50, Uncertain significance, Niemann-Pick disease, type C1
- L13P (p.Leu13Pro), Ensembl rs2145603735
- L14P (p.Leu14Pro), ExAC rs776078068, gnomAD rs776078068, REVEL 0.75, CADD 25.30
- L15M (p.Leu15Met), gnomAD rs1471054528, REVEL 0.24, CADD 22.30
- L15R (p.Leu15Arg), rs2059417979, ClinGen CA402041490, ClinVar RCV001280494, Ensembl rs2059417979, REVEL 0.60, CADD 24.40, Uncertain significance, Niemann-Pick disease, type C1
- L15F (p.Leu15Phe), rs2058428263, gnomAD 18-23529720-C-A, CADD 4.54
- L15V (p.Leu15Val), rs1598916961, gnomAD 18-23529722-A-C, CADD 0.62
- C16R (p.Cys16Arg), TOPMed rs2073238157, gnomAD rs2073238157, REVEL 0.41, CADD 22.50
- C16Y (p.Cys16Tyr), rs1407142143, ClinGen CA402041486, ClinVar RCV002004476, gnomAD rs1407142143, REVEL 0.36, CADD 22.40, Uncertain significance, Niemann-Pick disease, type C1
- P17S (p.Pro17Ser), rs2511394760, ClinGen CA402041479, ClinVar RCV002979549, Uncertain significance, Niemann-Pick disease, type C1
- A18G (p.Ala18Gly), Ensembl rs973277515, REVEL 0.23, CADD 21.20
- A18T (p.Ala18Thr), TOPMed rs1337785844, gnomAD rs1337785844, REVEL 0.34, CADD 21.40
- V20L (p.Val20Leu), rs1444708311, ClinGen CA402041448, NCI-TCGA Cosmic COSV5257, ClinVar RCV001754367, REVEL 0.42, CADD 26.00, Uncertain significance, not provided
- F21L (p.Phe21Leu), rs2145552491, ClinGen CA402041438, ClinVar RCV001931355, Ensembl rs2145552491, AlphaMissense 0.33, MetaLR 0.49, Uncertain significance, Niemann-Pick disease, type C1
- S22* (p.Ser22Ter), rs2511358187, ClinGen CA402041432, ClinVar RCV003605138, Pathogenic
- S22L (p.Ser22Leu), NCI-TCGA Cosmic COSV9934, Variant assessed as somatic; moderate impact.
- Q23* (p.Gln23Ter), NCI-TCGA Cosmic COSV9934, CADD 36.00, Variant assessed as somatic; high impact.
- Q23H (p.Gln23His), Ensembl rs2059233522, REVEL 0.29, CADD 12.70, Uncertain significance, not provided
- Q23R (p.Gln23Arg), gnomAD 18-23529703-T-C, CADD 3.71
- C25* (p.Cys25Ter), rs2511358085, ClinGen CA402041410, ClinVar RCV002309258, Likely pathogenic
- V26A (p.Val26Ala), rs2145296953, gnomAD 18-23529709-A-G, CADD 1.19
- W27* (p.Trp27Ter), rs2511358068, ClinGen CA402041399, ClinVar RCV002797169, CADD 36.00, Pathogenic
- Y28C (p.Tyr28Cys), rs1232191827, ClinGen CA402041389, ClinVar RCV002266261, ClinVar RCV003101493, REVEL 0.92, CADD 26.80, Uncertain significance, not specified; Niemann-Pick disease, type C1
- G29* (p.Gly29Ter), rs2145552346, ClinGen CA402041383, ClinVar RCV001383131, Ensembl rs2145552346, Pathogenic
- E30* (p.Glu30Ter), rs2059233326, ClinGen CA402041378, ClinVar RCV001263846, Ensembl rs2059233326, Likely pathogenic
- E30D (p.Glu30Asp), TOPMed rs1273070261, gnomAD rs1273070261, REVEL 0.64, CADD 18.60, Likely benign
- E30V (p.Glu30Val), rs776166330, ClinGen CA8913827, ClinVar RCV000734163, ClinVar RCV002485934, REVEL 0.76, CADD 23.30, Uncertain significance, not provided; Niemann-Pick disease, type C1
- C31R (p.Cys31Arg), rs2511357965, ClinGen CA402041371, ClinVar RCV003444429, Uncertain significance, Niemann-Pick disease, type C1
- G32R (p.Gly32Arg), ExAC rs765731953, gnomAD rs765731953, REVEL 0.87, CADD 26.70
- I33F (p.Ile33Phe), rs1244447626, ClinGen CA402041357, ClinVar RCV001955246, TOPMed rs1244447626, REVEL 0.28, CADD 13.70, Uncertain significance, Niemann-Pick disease, type C1
- I33T (p.Ile33Thr), gnomAD rs1360183867, REVEL 0.25, CADD 14.70
- A34V (p.Ala34Val), Ensembl rs1567981337, REVEL 0.33, CADD 22.00
- Y35F (p.Tyr35Phe), rs2511357860, ClinGen CA402041342, ClinVar RCV003067742, Uncertain significance, Niemann-Pick disease, type C1
- Y35H (p.Tyr35His), ExAC rs759005000, TOPMed rs759005000, gnomAD rs759005000, REVEL 0.11, CADD 7.25
- G36R (p.Gly36Arg), rs2059232891, ClinGen CA402041339, ClinVar RCV001874839, TOPMed rs2059232891, REVEL 0.45, CADD 22.40, Uncertain significance, Niemann-Pick disease, type C1
- D37A (p.Asp37Ala), ExAC rs776181190, TOPMed rs776181190, gnomAD rs776181190, Likely benign
- D37G (p.Asp37Gly), rs776181190, ClinGen CA8913824, ClinVar RCV001460913, ClinVar RCV004749694, REVEL 0.33, CADD 22.20, Conflicting interpretations, Niemann-Pick disease, type C1; not provided
- D37D (p.Asp37Asp), rs376719486, gnomAD 18-23529726-A-G, CADD 4.97
- K38E (p.Lys38Glu), rs2058428154, gnomAD 18-23529719-T-C, CADD 6.61
- Y40* (p.Tyr40Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- N41S (p.Asn41Ser), ExAC rs746658170, gnomAD rs746658170, REVEL 0.57, CADD 23.40
- E43K (p.Glu43Lys), rs138277307, ClinGen CA8913819, ClinVar RCV001579569, ESP rs138277307, REVEL 0.24, CADD 4.51, Likely benign, not provided
- S45F (p.Ser45Phe), Ensembl rs997482553
- G46D (p.Gly46Asp), rs1425737401, ClinGen CA402041264, ClinVar RCV001369382, TOPMed rs1425737401, REVEL 0.62, CADD 23.70, Uncertain significance, Niemann-Pick disease, type C1
- G46V (p.Gly46Val), TOPMed rs1425737401, gnomAD rs1425737401, REVEL 0.76, CADD 26.00, Uncertain significance
- P47L (p.Pro47Leu), TOPMed rs2059232372, REVEL 0.54, CADD 25.90
- P47H (p.Pro47His), rs868790540, gnomAD 18-23529712-G-T, REVEL 0.36, CADD 35.00
- P47T (p.Pro47Thr), gnomAD 18-23529714-T-TA, CADD 15.20
- K49* (p.Lys49Ter), rs1555642296, ClinGen CA658823795, ClinVar RCV000668007, Pathogenic
- P50L (p.Pro50Leu), rs1408235606, ClinGen CA402041237, ClinVar RCV003115666, gnomAD rs1408235606, REVEL 0.27, CADD 22.60, Uncertain significance, Niemann-Pick disease, type C1
- L51R (p.Leu51Arg), rs776866747, gnomAD 18-23529706-A-C, CADD 11.90
- L51V (p.Leu51Val), gnomAD 18-23529707-G-C, REVEL 0.50, CADD 24.70
- P52L (p.Pro52Leu), gnomAD rs2059232254, REVEL 0.29, CADD 22.90
- P52Q (p.Pro52Gln), gnomAD 18-23522903-G-T, CADD 2.00
- P52T (p.Pro52Thr), gnomAD 18-23522904-G-T, CADD 1.51
- K53N (p.Lys53Asn), NCI-TCGA Cosmic COSV5257, Variant assessed as somatic; moderate impact.
- D54G (p.Asp54Gly), Ensembl rs1045798708, REVEL 0.32, CADD 22.90
- G55A (p.Gly55Ala), ExAC rs754920859, gnomAD rs754920859, REVEL 0.58, CADD 21.60
- G55E (p.Gly55Glu), ExAC rs754920859, gnomAD rs754920859, REVEL 0.70, CADD 25.10
- G55R (p.Gly55Arg), TOPMed rs1418401182, gnomAD rs1418401182, REVEL 0.70, CADD 28.20
- G55G (p.Gly55Gly), gnomAD 18-23522905-G-A, CADD 0.74
- G55V (p.Gly55Val), gnomAD 18-23522906-C-A, CADD 7.77
- Y56C (p.Tyr56Cys), gnomAD rs1482926189, REVEL 0.68, CADD 24.80, Uncertain significance, Niemann-Pick disease, type C1; Inborn genetic diseases
- D57N (p.Asp57Asn), rs745994349, ClinGen CA8913816, ClinVar RCV003107001, ExAC rs745994349, REVEL 0.27, CADD 22.30, Uncertain significance, Niemann-Pick disease, type C1
- L58* (p.Leu58Ter), rs2511357450, ClinGen CA402041185, ClinVar RCV002308095, Pathogenic
- L58I (p.Leu58Ile), NCI-TCGA Cosmic COSV5257, Variant assessed as somatic; moderate impact.
- V59L (p.Val59Leu), rs1365313736, ClinGen CA402041179, ClinVar RCV001280493, TOPMed rs1365313736, REVEL 0.24, CADD 8.82, Uncertain significance, Niemann-Pick disease, type C1
- V59M (p.Val59Met), rs1365313736, ClinGen CA402041180, ClinVar RCV002638257, TOPMed rs1365313736, REVEL 0.23, CADD 19.00, Uncertain significance, Niemann-Pick disease, type C1
- Q60* (p.Gln60Ter), rs2511357416, ClinGen CA401787318, ClinVar RCV003022849, Pathogenic
- Q60H (p.Gln60His), rs145666943, ClinGen CA8913815, ClinVar RCV000728354, ClinVar RCV001125610, REVEL 0.66, CADD 26.00, Conflicting interpretations, Inborn genetic diseases; not provided; Niemann-Pick disease, type C1
- E61* (p.Glu61Ter), rs2059213874, ClinGen CA401786671, ClinVar RCV001198345, ClinVar RCV005641980, Pathogenic
- E61D (p.Glu61Asp), TOPMed rs2059213832, REVEL 0.46, CADD 13.50
- C63R (p.Cys63Arg), rs747049347, ClinGen CA8913794, ClinVar RCV003064507, ClinVar RCV006454320, REVEL 0.98, CADD 28.10, Likely pathogenic, Niemann-Pick disease, type C1; Niemann-Pick disease, type C
- C63Y (p.Cys63Tyr), rs2145544950, ClinGen CA401786634, ClinVar RCV001990349, Ensembl rs2145544950, AlphaMissense 0.98, MetaLR 0.97, Likely pathogenic, Niemann-Pick disease, type C1
- P64L (p.Pro64Leu), TOPMed rs2059213746
- G65A (p.Gly65Ala), Ensembl rs2059213681
- G65V (p.Gly65Val), Ensembl rs2059213681, REVEL 0.52, CADD 22.50, Uncertain significance, not provided
- F66L (p.Phe66Leu), rs1464483708, ClinGen CA401786580, ClinVar RCV002299357, TOPMed rs1464483708, REVEL 0.15, CADD 17.90, Uncertain significance, Niemann-Pick disease, type C1
- F66F (p.Phe66Phe), gnomAD 18-23522899-G-A, CADD 2.13
- F66S (p.Phe66Ser), gnomAD 18-23522900-A-G, CADD 4.33
- F67Y (p.Phe67Tyr), TOPMed rs1402286009, gnomAD rs1402286009, REVEL 0.37, CADD 22.00
- F68L (p.Phe68Leu), rs778177842, ClinGen CA8913793, ClinVar RCV000730915, ClinVar RCV001868960, REVEL 0.40, CADD 10.60, Uncertain significance, not provided; Niemann-Pick disease, type C1
- F68V (p.Phe68Val), TOPMed rs993533047, gnomAD rs993533047, REVEL 0.36, CADD 22.30
- G69D (p.Gly69Asp), rs1360920773, ClinGen CA401786529, ClinVar RCV002878776, TOPMed rs1360920773, REVEL 0.27, CADD 10.40, Likely benign, Inborn genetic diseases
- N70D (p.Asn70Asp), NCI-TCGA Cosmic COSV5258, REVEL 0.22, CADD 17.50, Variant assessed as somatic; moderate impact.
- N70S (p.Asn70Ser), rs200291759, ClinGen CA8913792, ClinVar RCV000731921, ClinVar RCV001369012, REVEL 0.28, CADD 18.60, Uncertain significance, not provided; Niemann-Pick disease, type C1
- N70Y (p.Asn70Tyr), rs2145544807, ClinGen CA401786520, ClinVar RCV001866541, Ensembl rs2145544807, AlphaMissense 0.20, MetaLR 0.63, Uncertain significance, Niemann-Pick disease, type C1
- N70H (p.Asn70His), rs557439505, gnomAD 18-23522898-T-G, CADD 0.39
- S72R (p.Ser72Arg), Ensembl rs1416579993
- S72S (p.Ser72Ser), gnomAD 18-23522893-G-A, CADD 0.34
- S72Y (p.Ser72Tyr), gnomAD 18-23522894-G-T, CADD 2.38
- L73F (p.Leu73Phe), rs2145544726, ClinGen CA401786485, ClinVar RCV003012280, AlphaMissense 0.09, MetaLR 0.23, Uncertain significance, Niemann-Pick disease, type C1
- L73I (p.Leu73Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L73V (p.Leu73Val), Ensembl rs2145544726
- C74W (p.Cys74Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in NPC1
- C74Y (p.Cys74Tyr), rs2059213166, UniProt VAR 043173, TOPMed rs2059213166, REVEL 0.93, CADD 26.20, Uncertain significance, not specified
- C75W (p.Cys75Trp), ExAC rs755230322, gnomAD rs755230322, REVEL 0.91, CADD 22.50
- D76E (p.Asp76Glu), TOPMed rs1387511417, Likely benign
- V77A (p.Val77Ala), gnomAD rs2059212939, REVEL 0.28, CADD 17.50
- V77D (p.Val77Asp), gnomAD rs2059212939, CADD 11.30
- V77I (p.Val77Ile), ExAC rs754380762, gnomAD rs754380762, CADD 0.16
- R78L (p.Arg78Leu), 1000Genomes rs373274825, ESP rs373274825, ExAC rs373274825, TOPMed rs373274825, REVEL 0.27, CADD 20.40, Uncertain significance
- R78Q (p.Arg78Gln), rs373274825, ClinGen CA8913786, ClinVar RCV000732048, ClinVar RCV000811491, REVEL 0.26, CADD 16.10, Conflicting interpretations, not provided; Niemann-Pick disease, type C1
- R78W (p.Arg78Trp), rs766822145, ClinGen CA8913787, ClinVar RCV001227331, ExAC rs766822145, REVEL 0.42, CADD 25.70, Uncertain significance, Niemann-Pick disease, type C1
- Q81H (p.Gln81His), Ensembl rs2059212754, REVEL 0.18, CADD 11.60
- T82I (p.Thr82Ile), gnomAD rs1248676783, REVEL 0.49, CADD 22.60
- D85E (p.Asp85Glu), rs2059212616, ClinGen CA401786402, ClinVar RCV002017718, TOPMed rs2059212616, REVEL 0.20, CADD 10.50, Uncertain significance, Niemann-Pick disease, type C1
- N86D (p.Asn86Asp), gnomAD rs1386653803, REVEL 0.51, CADD 23.10
- N86T (p.Asn86Thr), ExAC rs767216292, gnomAD rs767216292, Uncertain significance, not specified
- Q88H (p.Gln88His), Ensembl rs1599008867, Likely benign
- Q88L (p.Gln88Leu), TOPMed rs1599008875, gnomAD rs1599008875
- Q88R (p.Gln88Arg), TOPMed rs1599008875, gnomAD rs1599008875, REVEL 0.35, CADD 22.40
- P90R (p.Pro90Arg), rs2511352190, ClinVar RCV004586149, Likely pathogenic, Niemann-Pick disease, type C; Niemann-Pick disease, type C1
- L91V (p.Leu91Val), rs773809600, ClinGen CA401786369, NCI-TCGA Cosmic COSV5258, ClinVar RCV001893919, REVEL 0.43, CADD 18.50, Uncertain significance, Inborn genetic diseases; Niemann-Pick disease, type C1
- Q92* (p.Gln92Ter), rs2511352133, ClinGen CA401786363, ClinVar RCV003500204, CADD 40.00, Pathogenic, in NPC1
- Q92R (p.Gln92Arg), rs2145544354, ClinGen CA401786362, ClinVar RCV003064506, UniProt VAR 043174, REVEL 0.61, CADD 23.80, Pathogenic, Niemann-Pick disease, type C1
- S95F (p.Ser95Phe), ExAC rs762610198, gnomAD rs762610198, REVEL 0.64, CADD 24.60
- S95P (p.Ser95Pro), TOPMed rs1008764923, gnomAD rs1008764923, REVEL 0.77, CADD 24.60, Uncertain significance, not specified
- R96G (p.Arg96Gly), rs2511352031, ClinGen CA401786340, ClinVar RCV003329202, Conflicting interpretations, Niemann-Pick disease, type C; Niemann-Pick disease, type C1
- C97G (p.Cys97Gly), gnomAD rs1330533921, REVEL 0.97, CADD 33.00
- P98L (p.Pro98Leu), rs868281893, Ensembl rs868281893, AlphaMissense 0.82, MetaLR 0.98, Variant assessed as somatic; moderate impact.
- P98T (p.Pro98Thr), TOPMed rs1464167842, gnomAD rs1464167842, REVEL 0.96, CADD 25.60
- S99P (p.Ser99Pro), gnomAD rs1393471949, REVEL 0.69, CADD 24.30
- F101C (p.Phe101Cys), rs548191894, ClinGen CA8913762, ClinVar RCV000597242, ClinVar RCV001377830, REVEL 0.82, CADD 27.10, Conflicting interpretations, Niemann-Pick disease, type C; not provided; Niemann-Pick disease, type C1
- Y102* (p.Tyr102Ter), rs751249367, ClinGen CA401785903, ClinVar RCV000702851, ClinVar RCV001531279, CADD 38.00, Pathogenic
- N103K (p.Asn103Lys), rs2511341616, ClinGen CA401785877, ClinVar RCV003312409, Uncertain significance, not provided
- L104I (p.Leu104Ile), rs2145527400, ClinGen CA401785875, ClinVar RCV001991749, Ensembl rs2145527400, AlphaMissense 0.22, MetaLR 0.70, Uncertain significance, Niemann-Pick disease, type C1
- L105P (p.Leu105Pro), TOPMed rs2059164911, REVEL 0.65, CADD 24.60
- L105V (p.Leu105Val), TOPMed rs771946739, gnomAD rs771946739, REVEL 0.24, CADD 9.02
- N106D (p.Asn106Asp), rs2145527323, ClinGen CA401785847, ClinVar RCV001989470, Ensembl rs2145527323, AlphaMissense 0.23, MetaLR 0.71, Uncertain significance, Niemann-Pick disease, type C1
- C109* (p.Cys109Ter), rs2059164764, ClinGen CA401785739, ClinVar RCV001263845, Ensembl rs2059164764, Likely pathogenic
- E110Q (p.Glu110Gln), rs2145527241, ClinGen CA401785737, ClinVar RCV002050148, Ensembl rs2145527241, AlphaMissense 0.40, MetaLR 0.63, Uncertain significance, Niemann-Pick disease, type C1
- L111Q (p.Leu111Gln), Ensembl rs2059164673
- T112I (p.Thr112Ile), rs2511341460, ClinGen CA401785662, ClinVar RCV002295685, REVEL 0.93, CADD 27.10, Uncertain significance, Niemann-Pick disease, type C1
- C113* (p.Cys113Ter), rs2059164609, ClinGen CA401785620, ClinVar RCV001263844, Ensembl rs2059164609, CADD 31.00, Likely pathogenic, in NPC1
- C113R (p.Cys113Arg), rs120074136, ClinGen CA252503, ClinVar RCV000003112, ClinVar RCV002509143, AlphaMissense 0.99, MetaLR 0.98, Pathogenic/Likely pathogenic, Niemann-Pick disease, type C; Niemann-Pick disease, type C1
- C113Y (p.Cys113Tyr), rs2511341428, ClinGen CA401785632, ClinVar RCV002284102, Likely pathogenic, Niemann-Pick disease, type C1
- S114N (p.Ser114Asn), gnomAD rs1184328174, REVEL 0.73, CADD 24.60
- P115A (p.Pro115Ala), Ensembl rs748017608, REVEL 0.84, CADD 23.90
- P115L (p.Pro115Leu), gnomAD rs1472786529, REVEL 0.94, CADD 25.80
- R116* (p.Arg116Ter), rs144973225, ClinGen CA8913756, ClinVar RCV001092830, ClinVar RCV001386168, CADD 38.00, Pathogenic
- R116Q (p.Arg116Gln), rs140952850, ClinGen CA8913755, ClinVar RCV003026126, 1000Genomes rs140952850, REVEL 0.16, CADD 10.90, Uncertain significance, Niemann-Pick disease, type C1
- Q117* (p.Gln117Ter), rs2145527075, ClinGen CA401785531, ClinVar RCV001383912, Ensembl rs2145527075, CADD 40.00, Pathogenic
- Q117R (p.Gln117Arg), rs1567977251, ClinGen CA401785525, ClinVar RCV000705147, Ensembl rs1567977251, REVEL 0.95, CADD 26.40, Likely pathogenic, Niemann-Pick disease, type C1
- Q119E (p.Gln119Glu), gnomAD rs1294187402, REVEL 0.24, CADD 15.30
- F120Y (p.Phe120Tyr), NCI-TCGA Cosmic COSV5258, Variant assessed as somatic; moderate impact.
- L121F (p.Leu121Phe), ExAC rs772290631, TOPMed rs772290631, gnomAD rs772290631, REVEL 0.52, CADD 23.30
- N122S (p.Asn122Ser), TOPMed rs1448273242, REVEL 0.53, CADD 22.10
- T124K (p.Thr124Lys), Ensembl rs867274673, REVEL 0.65, CADD 22.90
- T124S (p.Thr124Ser), rs2511341207, ClinGen CA401785360, ClinVar RCV003292689, Uncertain significance, Inborn genetic diseases
- T126A (p.Thr126Ala), TOPMed rs1599002810, REVEL 0.37, CADD 18.80
- T126P (p.Thr126Pro), TOPMed rs1599002810
- T126S (p.Thr126Ser), NCI-TCGA TCGA novel, TOPMed rs1269273156, gnomAD rs1269273156, REVEL 0.30, CADD 19.90, Uncertain significance, Inborn genetic diseases
- E127Q (p.Glu127Gln), rs2511341135, ClinGen CA401785320, ClinVar RCV002623015, Uncertain significance, Niemann-Pick disease, type C1
- D128G (p.Asp128Gly), rs2059163907, ClinGen CA401785285, ClinVar RCV003018538, gnomAD rs2059163907, REVEL 0.18, CADD 22.00, Uncertain significance, Niemann-Pick disease, type C1
- D128H (p.Asp128His), rs868224237, ClinGen CA401785297, ClinVar RCV002697844, ClinVar RCV004765707, AlphaMissense 0.06, MetaLR 0.30, Uncertain significance, not specified; Inborn genetic diseases
- D128N (p.Asp128Asn), Ensembl rs868224237, REVEL 0.26, AlphaMissense 0.06
- D128Y (p.Asp128Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y129C (p.Tyr129Cys), Ensembl rs1363046191, REVEL 0.41, CADD 24.20
- V130I (p.Val130Ile), ExAC rs768728943, TOPMed rs768728943, gnomAD rs768728943, REVEL 0.24, CADD 3.53, Uncertain significance, Inborn genetic diseases
- P132A (p.Pro132Ala), Ensembl rs982522595
- P132T (p.Pro132Thr), Ensembl rs982522595
- V133G (p.Val133Gly), rs375039992, ClinGen CA8913750, ClinVar RCV000595676, ClinVar RCV001854086, REVEL 0.26, CADD 9.09, Uncertain significance, not provided; Niemann-Pick disease, type C1
- V133L (p.Val133Leu), rs2145526753, ClinGen CA401785169, ClinVar RCV001961286, Ensembl rs2145526753, REVEL 0.28, CADD 6.69, Uncertain significance, Niemann-Pick disease, type C1
Public NPC1 analysis runs
- NPC1 analysis run — NPC1 (1,771 variants) — completed 2026-08-18