NPC2 (P61916) variants and mutations
NPC2 (also known as P61916) is a human protein-coding gene encoding a NPC intracellular cholesterol transporter 2 protein. A lysosomal cholesterol-binding protein that works with NPC1 to move cholesterol out of late endosomes and lysosomes. Variants cause Niemann-Pick disease type C. This analysis covers 317 NPC2 variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes Niemann-Pick disease, type C2, Niemann-Pick disease type C, and hereditary disease. Example NPC2 variants include M1I, M1K, and M1R.
Variant analysis overview
- Gene: NPC2
- Protein: P61916
- UniProt accession: P61916
- Organism: Homo sapiens
- Variants analyzed: 317
- Variant scope: all variants
- Completed: 2026-10-09
Variant and mutation evidence
- Variant composition: 182 unspecified-consequence records; 4 stop lost; 2 stop retained variant; 41 synonymous variants; 84 missense variants; 2 in-frame deletions; 2 stop-gained variants; 10 frameshift variants; 2 splice-region variants; 5 substitution
- Prediction scores: 311 variants have prediction scores (98% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Niemann-Pick disease, type C2, Niemann-Pick disease type C, hereditary disease, Niemann-Pick disease, glaucoma, open-angle glaucoma, Niemann-Pick disease, type C1, dystonic disorder, Niemann-Pick disease type C, juvenile neurologic onset, Niemann-Pick disease type C, adult neurologic onset, Niemann-Pick disease type C, severe perinatal form, Niemann-Pick disease type C, late infantile neurologic onset.
Protein structure and variant hotspots
- Protein features: 3 post-translational modification sites.
- PTM context: 6 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.
Diseases linked to NPC2
Notable NPC2 variants
Examples include M1I, M1K, M1R, M1T, M1V, R2H, R2P, L4P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs483352893, ClinGen CA390377010, ClinVar RCV000673729, ClinGen CA269836, ESM-1b 1.00, AlphaMissense 0.35, Pathogenic, Niemann-Pick disease, type C; Niemann-Pick disease, type C2
- M1K (p.Met1Lys), rs1555346368, ClinGen CA390377017, ClinVar RCV003621234, ESM-1b 1.00, AlphaMissense 0.36, Pathogenic, Niemann-Pick disease, type C2
- M1R (p.Met1Arg), rs1555346368, ClinGen CA390377012, ClinVar RCV003009852, ESM-1b 1.00, AlphaMissense 0.27, Pathogenic, Niemann-Pick disease, type C2
- M1T (p.Met1Thr), rs1555346368, ClinGen CA390377014, ClinVar RCV000668937, NCI-TCGA Cosmic COSV5314, ESM-1b 1.00, AlphaMissense 0.41, Likely pathogenic, Niemann-Pick disease, type C2
- M1V (p.Met1Val), rs1555346369, ClinGen CA390377022, ClinVar RCV000670039, ESM-1b 1.00, AlphaMissense 0.13, Likely pathogenic, Niemann-Pick disease, type C2
- R2H (p.Arg2His), TOPMed rs1471655370, gnomAD rs1471655370, REVEL 0.27, ESM-1b 0.00, Uncertain significance
- R2P (p.Arg2Pro), rs1471655370, ClinGen CA390377003, ClinVar RCV002804077, REVEL 0.55, ESM-1b 0.54, Uncertain significance, Inborn genetic diseases
- L4P (p.Leu4Pro), Ensembl rs1436257362, ESM-1b 0.60, AlphaMissense 0.12
- A5E (p.Ala5Glu), gnomAD rs1322133696, REVEL 0.46, ESM-1b 1.00
- A5T (p.Ala5Thr), rs2506115644, ClinGen CA390376956, ClinVar RCV002766147, REVEL 0.24, ESM-1b 0.00, Uncertain significance, Niemann-Pick disease, type C2
- T7I (p.Thr7Ile), TOPMed rs1363601263, gnomAD rs1363601263, REVEL 0.29, ESM-1b 0.00
- T7K (p.Thr7Lys), TOPMed rs1363601263, gnomAD rs1363601263, REVEL 0.39, ESM-1b 1.00
- F8L (p.Phe8Leu), Ensembl rs2086796595, REVEL 0.30, ESM-1b 0.00
- L9V (p.Leu9Val), TOPMed rs1033995785, ESM-1b 0.00, AlphaMissense 0.08, Likely benign
- A12E (p.Ala12Glu), TOPMed rs981046790, gnomAD rs981046790, REVEL 0.60, ESM-1b 1.00
- A12S (p.Ala12Ser), TOPMed rs970145012, gnomAD rs970145012, ESM-1b 0.00, AlphaMissense 0.13, Uncertain significance
- A12T (p.Ala12Thr), TOPMed rs970145012, gnomAD rs970145012, REVEL 0.31, ESM-1b 0.00, Uncertain significance, Niemann-Pick disease, type C2
- A12V (p.Ala12Val), TOPMed rs981046790, gnomAD rs981046790, REVEL 0.24, ESM-1b 0.00
- L13P (p.Leu13Pro), rs147602717, ClinGen CA7268216, ClinVar RCV002015465, ClinVar RCV005645352, REVEL 0.62, ESM-1b 1.00, Uncertain significance, not provided; NPC2-related disorder; Niemann-Pick disease, type C2
- T15S (p.Thr15Ser), TOPMed rs992831907, ESM-1b 0.00, AlphaMissense 0.08
- A16S (p.Ala16Ser), gnomAD rs1210749225, REVEL 0.16, ESM-1b 0.00
- A17G (p.Ala17Gly), ExAC rs764017800, gnomAD rs764017800, ESM-1b 0.00, AlphaMissense 0.11
- A17T (p.Ala17Thr), ESP rs145302203, TOPMed rs145302203, ESM-1b 0.00, AlphaMissense 0.10
- A17V (p.Ala17Val), ExAC rs764017800, gnomAD rs764017800, REVEL 0.17, ESM-1b 0.00
- A19D (p.Ala19Asp), rs369392502, ClinGen CA7268214, cosmic curated COSV99467, ClinVar RCV001115296, REVEL 0.75, ESM-1b 1.00, Uncertain significance, Niemann-Pick disease, type C2; Niemann-Pick disease, type C1
- A19V (p.Ala19Val), ESP rs369392502, ExAC rs369392502, TOPMed rs369392502, gnomAD rs369392502, REVEL 0.64, ESM-1b 0.03, Uncertain significance
- E20* (p.Glu20Ter), rs80358260, ClinGen CA340788, ClinVar RCV000008998, ClinVar RCV000586093, CADD 36.00, Pathogenic
- E20K (p.Glu20Lys), rs80358260, ClinGen CA7268212, ClinVar RCV001278151, ESP rs80358260, REVEL 0.59, ESM-1b 0.00, Uncertain significance, Niemann-Pick disease, type C2
- E20X, rs80358260, Conflicting interpretations
- P21L (p.Pro21Leu), ExAC rs776749539, TOPMed rs776749539, gnomAD rs776749539, REVEL 0.55, ESM-1b 0.33, Uncertain significance
- P21Q (p.Pro21Gln), rs776749539, ClinGen CA390376677, ClinVar RCV003083950, REVEL 0.57, ESM-1b 0.00, Uncertain significance, Niemann-Pick disease, type C2
- V22A (p.Val22Ala), rs868238817, []
- Q23* (p.Gln23Ter), rs2506115406, ClinGen CA390376662, ClinVar RCV003337786, Likely pathogenic
- Q23R (p.Gln23Arg), ExAC rs770988699, gnomAD rs770988699, REVEL 0.15, ESM-1b 0.00
- F24L (p.Phe24Leu), Ensembl rs1566605868, ESM-1b 1.00, AlphaMissense 0.99, Likely benign
- K25R (p.Lys25Arg), rs2506115373, ClinGen CA390376646, ClinVar RCV003288435, ClinVar RCV006472282, ESM-1b 0.02, AlphaMissense 0.08, Uncertain significance, Inborn genetic diseases; Niemann-Pick disease, type C2
- C27T (p.Cys27Thr), NCI-TCGA Cosmic COSV5314, cosmic curated COSV53143, Variant assessed as somatic; moderate impact.
- C27G (p.Cys27Gly), gnomAD rs1293797925, REVEL 0.85, ESM-1b 1.00
- G28T (p.Gly28Thr), rs483352893, ClinGen CA7268220, ClinVar RCV002613296, MetaLR 0.84, MetaSVM 0.83, Pathogenic
- G28D (p.Gly28Asp), TOPMed rs1443294832, gnomAD rs1443294832, REVEL 0.77, ESM-1b 1.00, Uncertain significance, Inborn genetic diseases
- S29C (p.Ser29Cys), rs753010998, ClinGen CA7268193, ClinVar RCV001909621, ClinVar RCV004042815, REVEL 0.76, ESM-1b 1.00, Uncertain significance, Inborn genetic diseases; Niemann-Pick disease, type C2
- V30M (p.Val30Met), rs151220873, ClinGen CA249909, cosmic curated COSV99467, ClinVar RCV000162102, REVEL 0.49, ESM-1b 0.00, Benign/Likely benign, not specified; not provided; Niemann-Pick disease, type C2
- D31Y (p.Asp31Tyr), Ensembl rs868810641, REVEL 0.35, ESM-1b 0.00
- G32R (p.Gly32Arg), rs2506107358, ClinGen CA390532842, ClinVar RCV003621381, REVEL 0.78, ESM-1b 1.00, Uncertain significance, Niemann-Pick disease, type C2
- I34V (p.Ile34Val), rs2506107337, ClinGen CA390532829, ClinVar RCV003619455, REVEL 0.09, ESM-1b 0.00, Uncertain significance, Niemann-Pick disease, type C2
- K35R (p.Lys35Arg), TOPMed rs1235656880, gnomAD rs1235656880, REVEL 0.22, ESM-1b 0.76
- E36* (p.Glu36Ter), rs2139670174, ClinGen CA390532813, ClinVar RCV001970052, Ensembl rs2139670174, CADD 37.00, Pathogenic
- V37A (p.Val37Ala), gnomAD rs2086712978, REVEL 0.87, ESM-1b 0.90
- V39A (p.Val39Ala), TOPMed rs1334912147, gnomAD rs1334912147, REVEL 0.86, ESM-1b 1.00
- V39M (p.Val39Met), rs80358261, ClinGen CA340794, cosmic curated COSV10458, ClinVar RCV000009004, REVEL 0.80, ESM-1b 1.00, Uncertain significance, not provided; Niemann-Pick disease, type C2
- S40* (p.Ser40Ter), rs2506107289, ClinGen CA2582341761, ClinVar RCV003333265, Likely pathogenic
- T44P (p.Thr44Pro), rs2139670146, ClinGen CA390532760, ClinVar RCV002381044, Ensembl rs2139670146, ESM-1b 0.68, AlphaMissense 0.31, Uncertain significance, Inborn genetic diseases
- Q45* (p.Gln45Ter), rs80358262, ClinGen CA342106, ClinVar RCV000020643, ClinVar RCV001193595, CADD 34.00, Pathogenic
- C47* (p.Cys47Ter), rs80358263, ClinGen CA342108, ClinVar RCV000020644, ClinVar RCV002513144, CADD 34.00, Pathogenic, in NPC2
- C47F (p.Cys47Phe), rs1555345993, ClinGen CA390532736, ClinVar RCV000664587, UniProt VAR 043304, REVEL 0.88, ESM-1b 1.00, Uncertain significance, Niemann-Pick disease, type C2
- C47R (p.Cys47Arg), Ensembl rs2139670135, ESM-1b 1.00, AlphaMissense 0.99
- Q48* (p.Gln48Ter), rs2086712538, ClinGen CA390532732, ClinVar RCV001263851, Ensembl rs2086712538, CADD 32.00, Likely pathogenic
- Q48P (p.Gln48Pro), TOPMed rs1469718807, gnomAD rs1469718807, REVEL 0.28, ESM-1b 0.00
- L49P (p.Leu49Pro), rs1310092921, ClinGen CA390532723, ClinVar RCV003088869, TOPMed rs1310092921, REVEL 0.84, ESM-1b 1.00, Uncertain significance, Niemann-Pick disease, type C2
- S50N (p.Ser50Asn), TOPMed rs993005043, gnomAD rs993005043, REVEL 0.19, ESM-1b 0.00
- G52A (p.Gly52Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G52* (p.Gly52Ter), rs2506107168, ClinGen CA390532704, ClinVar RCV002309360, CADD 37.00, Likely pathogenic
- Q53* (p.Gln53Ter), rs2086712337, ClinGen CA390532698, ClinVar RCV001170047, Ensembl rs2086712337, CADD 36.00, Pathogenic
- S54C (p.Ser54Cys), rs2506107142, ClinGen CA390532689, ClinVar RCV002829491, REVEL 0.66, ESM-1b 1.00, Uncertain significance, Niemann-Pick disease, type C2
- S54P (p.Ser54Pro), rs767080399, ClinGen CA7268188, ClinVar RCV001906649, ExAC rs767080399, REVEL 0.57, ESM-1b 0.28, Uncertain significance, Niemann-Pick disease, type C2
- Y55* (p.Tyr55Ter), rs2086712268, ClinGen CA390532680, ClinVar RCV001963172, ClinVar RCV006697568, CADD 35.00, Pathogenic
- V57I (p.Val57Ile), rs774036281, ClinGen CA7268186, ClinVar RCV001039143, ClinVar RCV005682464, REVEL 0.21, ESM-1b 0.00, Uncertain significance, Inborn genetic diseases; NPC2-related disorder; Niemann-Pick disease, type C2
- T60I (p.Thr60Ile), gnomAD rs1390815745, REVEL 0.76, ESM-1b 1.00
- T62A (p.Thr62Ala), ExAC rs748877887, gnomAD rs748877887, REVEL 0.20, ESM-1b 1.00
- T62I (p.Thr62Ile), TOPMed rs2086712073, REVEL 0.27, ESM-1b 0.17
- N64D (p.Asn64Asp), TOPMed rs2086712042, REVEL 0.13, ESM-1b 0.00
- N64I (p.Asn64Ile), rs1391222276, ClinGen CA390532608, ClinVar RCV001970713, TOPMed rs1391222276, REVEL 0.27, ESM-1b 1.00, Uncertain significance, Niemann-Pick disease, type C2
- N64T (p.Asn64Thr), TOPMed rs1391222276, gnomAD rs1391222276, REVEL 0.10, ESM-1b 0.00, Uncertain significance
- I65S (p.Ile65Ser), ExAC rs755819257, TOPMed rs755819257, gnomAD rs755819257, REVEL 0.22, ESM-1b 0.31
- I65T (p.Ile65Thr), ExAC rs755819257, TOPMed rs755819257, gnomAD rs755819257, REVEL 0.19, ESM-1b 0.00
- I65V (p.Ile65Val), gnomAD 14-74484585-T-C, REVEL 0.09, ESM-1b 0.00
- I65F (p.Ile65Phe), gnomAD 14-74484585-T-A, REVEL 0.18, ESM-1b 0.01
- Q66L (p.Gln66Leu), TOPMed rs2086689798, REVEL 0.23, ESM-1b 0.00, Uncertain significance, NPC2-related disorder
- S67P (p.Ser67Pro), rs11694, ClinGen CA340793, ClinVar RCV000009003, UniProt VAR 015849, ESM-1b 1.00, AlphaMissense 0.97, Pathogenic, Niemann-Pick disease, type C2
- K68* (p.Lys68Ter), ExAC rs750426509, TOPMed rs750426509, gnomAD rs750426509, AlphaMissense 0.09, MetaLR 0.41, Likely pathogenic
- K68E (p.Lys68Glu), rs750426509, ClinGen CA390532585, ClinVar RCV001966904, ExAC rs750426509, ESM-1b 0.12, AlphaMissense 0.09, Uncertain significance, Niemann-Pick disease, type C2
- K68I (p.Lys68Ile), ExAC rs767330361, TOPMed rs767330361, gnomAD rs767330361, REVEL 0.31, ESM-1b 1.00, Uncertain significance, Inborn genetic diseases
- S69* (p.Ser69Ter), ExAC rs769572626, gnomAD rs769572626, CADD 22.90
- S69N (p.Ser69Asn), Ensembl rs2086689639, REVEL 0.05, ESM-1b 0.00
- S69S (p.Ser69Ser), rs970173671, gnomAD 14-74484571-G-A, CADD 2.59
- S70G (p.Ser70Gly), Ensembl rs1303114527, ESM-1b 0.56, AlphaMissense 0.24
- S70I (p.Ser70Ile), gnomAD 14-74484569-C-A, REVEL 0.41, ESM-1b 0.00
- K71R (p.Lys71Arg), rs142075589, ClinGen CA7268167, ClinVar RCV000335990, ClinVar RCV000595194, REVEL 0.33, ESM-1b 0.41, Uncertain significance, Inborn genetic diseases; not provided; Niemann-Pick disease, type C2
- A72V (p.Ala72Val), rs1242060760, NCI-TCGA Cosmic COSV5314, cosmic curated COSV53143, gnomAD rs1242060760, REVEL 0.49, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- A72A (p.Ala72Ala), rs773861377, gnomAD 14-74484562-G-A, CADD 2.72
- A72D (p.Ala72Asp), gnomAD 14-74484563-G-T, REVEL 0.72, ESM-1b 1.00
- V73M (p.Val73Met), rs747314957, ClinGen CA263660967, ClinVar RCV002995885, TOPMed rs747314957, REVEL 0.38, ESM-1b 1.00, Uncertain significance, Niemann-Pick disease, type C2
- V73V (p.Val73Val), rs1281836334, gnomAD 14-74484559-C-A, CADD 1.23
- V74V (p.Val74Val), rs763523833, gnomAD 14-74484556-C-T, CADD 2.25
- H75L (p.His75Leu), ESP rs369221608, ExAC rs369221608, TOPMed rs369221608, gnomAD rs369221608, REVEL 0.54, ESM-1b 1.00
- H75R (p.His75Arg), ESP rs369221608, ExAC rs369221608, TOPMed rs369221608, gnomAD rs369221608, REVEL 0.53, ESM-1b 0.00
- H75Y (p.His75Tyr), rs762621803, ClinGen CA7268164, ClinVar RCV004516866, ExAC rs762621803, REVEL 0.20, ESM-1b 0.65, Uncertain significance, Inborn genetic diseases
- G76D (p.Gly76Asp), TOPMed rs978355274, ESM-1b 1.00, AlphaMissense 0.99
- I77V (p.Ile77Val), ExAC rs771374515, gnomAD rs771374515, REVEL 0.10, ESM-1b 0.00
- I77M (p.Ile77Met), gnomAD 14-74484547-G-C, REVEL 0.39, ESM-1b 1.00
- I77F (p.Ile77Phe), gnomAD 14-74484549-T-A, REVEL 0.53, ESM-1b 1.00
- L78P (p.Leu78Pro), ExAC rs747302449, TOPMed rs747302449, gnomAD rs747302449, REVEL 0.60, ESM-1b 1.00
- L78V (p.Leu78Val), rs2506104611, ClinGen CA390532522, ClinVar RCV002781030, REVEL 0.15, ESM-1b 0.00, Uncertain significance, Niemann-Pick disease, type C2
- M79T (p.Met79Thr), Ensembl rs1487074303, REVEL 0.27, ESM-1b 0.24
- M79L (p.Met79Leu), gnomAD 14-74484543-T-A, REVEL 0.20, ESM-1b 0.00
- G80G (p.Gly80Gly), rs773836291, gnomAD 14-74484538-G-A, CADD 2.31
- V81A (p.Val81Ala), TOPMed rs2086688924, gnomAD rs2086688924, REVEL 0.42, ESM-1b 0.73
- V81F (p.Val81Phe), ExAC rs772444418, TOPMed rs772444418, gnomAD rs772444418, REVEL 0.31, ESM-1b 0.88, Uncertain significance
- V81I (p.Val81Ile), rs772444418, ClinGen CA7268159, ClinVar RCV002647806, ExAC rs772444418, REVEL 0.07, ESM-1b 0.00, Uncertain significance, Niemann-Pick disease, type C2
- P82P (p.Pro82Pro), gnomAD 14-74484532-T-G, CADD 4.52
- P82A (p.Pro82Ala), gnomAD 14-74484534-G-C, REVEL 0.27, ESM-1b 0.96
- V83F (p.Val83Phe), TOPMed rs1399142643, gnomAD rs1399142643, REVEL 0.55, ESM-1b 0.22
- V83L (p.Val83Leu), TOPMed rs1399142643, gnomAD rs1399142643, REVEL 0.15, ESM-1b 0.00
- P84L (p.Pro84Leu), TOPMed rs1432578885, gnomAD rs1432578885, REVEL 0.73, ESM-1b 1.00
- P84P (p.Pro84Pro), gnomAD 14-74484526-G-C, CADD 10.30
- P84A (p.Pro84Ala), gnomAD 14-74484528-G-C, REVEL 0.62, ESM-1b 1.00
- P86L (p.Pro86Leu), rs4688, UniProt VAR 011899, TOPMed rs4688, ESM-1b 0.88, AlphaMissense 0.27
- P86T (p.Pro86Thr), Ensembl rs895468257, ESM-1b 0.23, AlphaMissense 0.22
- I87F (p.Ile87Phe), rs779138735, ClinGen CA390532469, ClinVar RCV002750116, ESM-1b 1.00, AlphaMissense 0.22, Uncertain significance, Niemann-Pick disease, type C2
- I87V (p.Ile87Val), ExAC rs779138735, gnomAD rs779138735, REVEL 0.25, ESM-1b 0.00, Uncertain significance
- I87I (p.Ile87Ile), gnomAD 14-74484517-A-G, CADD 8.65
- P88L (p.Pro88Leu), TOPMed rs1020827082, ESM-1b 1.00, AlphaMissense 0.32
- P88S (p.Pro88Ser), rs2139668049, ClinGen CA390532463, ClinVar RCV001757977, ClinVar RCV002032783, REVEL 0.38, ESM-1b 1.00, Uncertain significance, not provided; Niemann-Pick disease, type C2
- P88P (p.Pro88Pro), rs1011669605, gnomAD 14-74484514-A-G, CADD 13.00
- E89Q (p.Glu89Gln), gnomAD rs2086688575, REVEL 0.24, ESM-1b 0.00
- E89E (p.Glu89Glu), rs1391975409, gnomAD 14-74484511-C-T, CADD 8.35
- E89D (p.Glu89Asp), gnomAD 14-74484511-C-A, REVEL 0.20, ESM-1b 0.00
- P90H (p.Pro90His), TOPMed rs1301761255, ESM-1b 1.00, AlphaMissense 0.34
- P90L (p.Pro90Leu), TOPMed rs1301761255, ESM-1b 1.00, AlphaMissense 0.25
- P90P (p.Pro90Pro), rs758503440, gnomAD 14-74484508-A-G, CADD 5.24
- D91N (p.Asp91Asn), rs148607507, ClinGen CA7268155, ClinVar RCV000338408, ClinVar RCV000763944, REVEL 0.42, ESM-1b 0.00, Uncertain significance, Inborn genetic diseases; not provided; Niemann-Pick disease, type C2
- D91D (p.Asp91Asp), rs151071820, gnomAD 14-74484505-A-G, CADD 7.36
- D91Y (p.Asp91Tyr), gnomAD 14-74484507-C-A, REVEL 0.88, ESM-1b 1.00
- G92G (p.Gly92Gly), gnomAD 14-74484502-A-G, CADD 9.92
- C93F (p.Cys93Phe), rs143960270, ClinGen CA7268153, ClinVar RCV001580747, ClinVar RCV005237922, REVEL 0.96, ESM-1b 1.00, Conflicting interpretations, Niemann-Pick disease, type C2; not specified
- C93S (p.Cys93Ser), ESP rs143960270, ExAC rs143960270, gnomAD rs143960270, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, in NPC2
- C93C (p.Cys93Cys), rs750185667, gnomAD 14-74484499-A-G, CADD 12.80
- C93Y (p.Cys93Tyr), gnomAD 14-74484500-C-T, REVEL 0.95, ESM-1b 1.00
- C93R (p.Cys93Arg), gnomAD 14-74484501-A-G, REVEL 0.97, ESM-1b 1.00
- K94* (p.Lys94Ter), rs1376058648, ClinGen CA615195087, ClinVar RCV001388699, ClinVar RCV003120598, CADD 32.00, Pathogenic
- K94N (p.Lys94Asn), gnomAD 14-74484496-C-G, REVEL 0.49, ESM-1b 1.00
- K94E (p.Lys94Glu), gnomAD 14-74484498-T-C, REVEL 0.54, ESM-1b 1.00
- S95N (p.Ser95Asn), gnomAD 14-74484494-C-T, REVEL 0.45, ESM-1b 1.00
- G96R (p.Gly96Arg), TOPMed rs996404779, gnomAD rs996404779, REVEL 0.78, ESM-1b 1.00
- N98H (p.Asn98His), rs142858704, ClinGen CA7268151, ClinVar RCV000439975, ClinVar RCV000763943, REVEL 0.09, ESM-1b 0.94, Uncertain significance, NPC2-related disorder; Inborn genetic diseases; not provided
- N98T (p.Asn98Thr), TOPMed rs2086688077, ESM-1b 0.00, AlphaMissense 0.07
- N98N (p.Asn98Asn), rs1192101137, gnomAD 14-74484484-G-A, CADD 9.52
- N98K (p.Asn98Lys), gnomAD 14-74484484-G-C, REVEL 0.17, ESM-1b 0.00
- C99* (p.Cys99Ter), rs2086687936, ClinGen CA390532385, ClinVar RCV001263850, Ensembl rs2086687936, AlphaMissense 0.96, MetaLR 1.00, Likely pathogenic, in NPC2
- C99F (p.Cys99Phe), rs2506104453, ClinGen CA390532386, ClinVar RCV003022697, ESM-1b 1.00, AlphaMissense 0.97, Uncertain significance, Niemann-Pick disease, type C2
- C99R (p.Cys99Arg), rs80358264, ClinGen CA342111, ClinVar RCV000020646, ClinVar RCV003398552, REVEL 0.96, ESM-1b 1.00, Pathogenic, Niemann-Pick disease, type C2; Niemann-Pick disease, type C
- C99W (p.Cys99Trp), rs2086687936, ClinGen CA390532384, ClinVar RCV001806310, Ensembl rs2086687936, ESM-1b 1.00, AlphaMissense 0.96, Likely pathogenic, Niemann-Pick disease, type C2
- P100T (p.Pro100Thr), TOPMed rs2086687901, ESM-1b 1.00, AlphaMissense 0.68, Uncertain significance, Niemann-Pick disease, type C2
- P100P (p.Pro100Pro), rs2139667977, gnomAD 14-74484478-A-G, CADD 13.50
- I101M (p.Ile101Met), rs2506104439, ClinGen CA390532371, ClinVar RCV003067900, REVEL 0.72, ESM-1b 1.00, Uncertain significance, Niemann-Pick disease, type C2
- I101L (p.Ile101Leu), gnomAD 14-74484477-T-G, REVEL 0.44, ESM-1b 0.00
- Q102* (p.Gln102Ter), rs2086687862, ClinGen CA390532368, ClinVar RCV001263849, Ensembl rs2086687862, Likely pathogenic
- Q102R (p.Gln102Arg), rs930750290, ClinGen CA263660912, ClinVar RCV001878129, ClinVar RCV002553534, REVEL 0.13, ESM-1b 0.40, Uncertain significance, Niemann-Pick disease, type C2; NPC2-related disorder; Inborn genetic diseases
- D104D (p.Asp104Asp), rs751455041, gnomAD 14-74484466-G-A, CADD 9.22
- D104Y (p.Asp104Tyr), gnomAD 14-74484468-C-A, REVEL 0.50, ESM-1b 1.00
- K105N (p.Lys105Asn), gnomAD rs1220089148, REVEL 0.21, ESM-1b 0.00, Likely benign
- K105D (p.Lys105Asp), gnomAD 14-74484463-CTT-C, CADD 27.80
- K105E (p.Lys105Glu), gnomAD 14-74484465-T-C, REVEL 0.20, ESM-1b 0.00
- T106S (p.Thr106Ser), TOPMed rs1221662658, gnomAD rs1221662658, REVEL 0.14, ESM-1b 0.00
- T106T (p.Thr106Thr), rs763613633, gnomAD 14-74484460-G-C, CADD 10.90
- Y107C (p.Tyr107Cys), gnomAD 14-74484458-T-C, REVEL 0.76, ESM-1b 1.00
- S108I (p.Ser108Ile), TOPMed rs2086687611, REVEL 0.36, ESM-1b 0.29
- S108G (p.Ser108Gly), gnomAD 14-74484456-T-C, REVEL 0.25, ESM-1b 0.52
- L110L (p.Leu110Leu), rs762424530, gnomAD 14-74484448-C-G, CADD 11.50
- L110P (p.Leu110Pro), gnomAD 14-74484449-A-G, REVEL 0.49, ESM-1b 1.00
- L110R (p.Leu110Arg), gnomAD 14-74484449-A-C, REVEL 0.34, ESM-1b 1.00
- N111K (p.Asn111Lys), rs757377148, ClinGen CA7268147, ClinVar RCV000665380, ExAC rs757377148, REVEL 0.53, ESM-1b 1.00, Uncertain significance, Niemann-Pick disease, type C2
- N111I (p.Asn111Ile), rs80358265, gnomAD 14-74484445-AT-A, CADD 29.40
- N111T (p.Asn111Thr), gnomAD 14-74484446-T-G, REVEL 0.18, ESM-1b 1.00
- K112* (p.Lys112Ter), rs2086687425, ClinGen CA390532293, ClinVar RCV001263848, Ensembl rs2086687425, Likely pathogenic
- K112R (p.Lys112Arg), rs2506104391, ClinGen CA390532291, ClinVar RCV002321048, ESM-1b 0.00, AlphaMissense 0.10, Uncertain significance, Inborn genetic diseases
- K112N (p.Lys112Asn), gnomAD 14-74484442-T-G, REVEL 0.48, ESM-1b 0.00
- K112Q (p.Lys112Gln), gnomAD 14-74484444-T-G, REVEL 0.22, ESM-1b 0.00
- L113L (p.Leu113Leu), gnomAD 14-74484439-T-C, CADD 1.75
- L113I (p.Leu113Ile), gnomAD 14-74484441-G-T, REVEL 0.54, ESM-1b 0.66
Public NPC2 analysis runs
- NPC2 analysis run — NPC2 (317 variants) — completed 2026-10-09