NPC2 p.Gln131=
c.393G>A · rs2506099932 · VCV2102258
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Niemann-Pick disease, type C2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.015 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.6 | GERP -2.7 |
| Overall | ||
| CADD | 0.292 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- NPC2
- Protein
- p.Gln131=
- Coding
- c.393G>A
- MANE Select
- NM_006432
- dbSNP
- rs2506099932
- Type
- single nucleotide variant
- Location
- chr14:74480750 (GRCh38)
- Gene constraint
- LOEUF 1.422 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.88 · 2 PDB
- Residue 131
- a β-strand
Disease context
Niemann-Pick disease, type C2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Niemann-Pick disease type C (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- NPC2 c.190+5G>A Pathogenic/Likely pathogenic ★★ same condition
- NPC2 p.Cys47Ter Pathogenic ★★ same condition
- NPC2 p.Cys99Arg Pathogenic ★★ same condition
- NPC2 p.Gln45Ter Pathogenic/Likely pathogenic ★★ same condition
- NPC2 p.Glu118Ter Pathogenic ★★ same condition
- NPC2 p.Glu20Ter Pathogenic ★★ same condition
- NPC2 p.Met1Ile Pathogenic/Likely pathogenic ★★ same condition
- NPC2 p.Pro120Ser Pathogenic/Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/npc2-p-gln131 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown