NPC1 p.Val780fs
c.2336dup · VCV3774957
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
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 15 of 25 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -3 | GERP -3.9 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- NPC1
- Protein
- p.Val780fs
- Coding
- c.2336dup
- MANE Select
- NM_000271
- Type
- Duplication
- Location
- chr18:23541342 (GRCh38)
- Gene constraint
- LOEUF 0.676 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.35 · 20 PDB
- Residue 780
- the ssd domain; an α-helix
Similar variants
- NPC1 p.Val780Gly Uncertain significance ★ ⚠ same residue
- NPC1 p.Val780Met Uncertain significance ★ ⚠ same residue
- NPC1 c.3591+2dup Pathogenic/Likely pathogenic ★★ same type
- NPC1 p.Ala1192fs Pathogenic/Likely pathogenic ★★ same type
- NPC1 p.Asn1137fs Pathogenic/Likely pathogenic ★★ same type
- NPC1 p.Asn589Ter Pathogenic ★★ same type
- NPC1 p.Asp325fs Pathogenic ★★ same type
- NPC1 p.Glu895fs Pathogenic ★★ same type
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-val780fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown