NPC1 p.Asp54fs
c.155_156insT · VCV4818046
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Niemann-Pick disease, type C1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 25 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -6.1 | GERP -3.8 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- NPC1
- Protein
- p.Asp54fs
- Coding
- c.155_156insT
- MANE Select
- NM_000271
- Type
- Insertion
- Location
- chr18:23573476 (GRCh38)
- Gene constraint
- LOEUF 0.676 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.35 · 20 PDB
- Residue 54
- an α-helix; a disulfide bond
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.Glu985fs Pathogenic/Likely pathogenic ★★ same condition
- NPC1 c.1947+10_1947+11insGGGT Benign/Likely benign ★★ same condition
- NPC1 c.1947+10_1947+11insT Likely benign ★★ same condition
- NPC1 c.1947+11_1947+12insGGGA Likely benign ★★ same condition
- NPC1 c.1947+11_1947+12insGGGT Benign/Likely benign ★★ same condition
- NPC1 c.1947+13_1947+14insGGC Likely benign ★★ same condition
- NPC1 c.1947+13_1947+14insGGT Likely benign ★★ same condition
- NPC1 c.1947+13_1947+14insT Likely benign ★★ 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-asp54fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown