NPC1 p.Phe1139=
c.3417T>C · rs2145350366 · VCV1550252
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 C1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -3.6 |
| Overall | ||
| CADD | 3.511 | 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
- NPC1
- Protein
- p.Phe1139=
- Coding
- c.3417T>C
- MANE Select
- NM_000271
- dbSNP
- rs2145350366
- Type
- single nucleotide variant
- Location
- chr18:23535529 (GRCh38)
- Gene constraint
- LOEUF 0.676 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.35 · 20 PDB
- Residue 1139
- an α-helix
Disease context
Niemann-Pick disease, type C1 — 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
- NPC1 p.Phe1139fs Likely pathogenic same residue
- NPC1 c.1554-1009G>A Pathogenic ★★ same condition
- NPC1 c.1757+1G>A Likely pathogenic ★★ same condition
- NPC1 c.1947+5G>C Pathogenic/Likely pathogenic ★★ same condition
- NPC1 c.2130+1G>A Pathogenic ★★ same condition
- NPC1 c.2245+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NPC1 c.2246-2A>G Pathogenic/Likely pathogenic ★★ same condition
- NPC1 c.2515-2A>G 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/npc1-p-phe1139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown