NPC1 p.Ala885=
c.2655G>A · rs544601083 · VCV598414
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -11 | GERP -3.9 |
| Overall | ||
| CADD | 1.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00155%
25/1,614,012 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| East Asian | 0.00223% | 44,896 |
| European (non-Finnish) | 0.00195% | 51,305 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- NPC1
- Protein
- p.Ala885=
- Coding
- c.2655G>A
- MANE Select
- NM_000271
- dbSNP
- rs544601083
- Type
- single nucleotide variant
- Location
- chr18:23539951 (GRCh38)
- Gene constraint
- LOEUF 0.676 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.35 · 20 PDB
Similar variants
- NPC1 p.Ala885Val Uncertain significance ★★ ⚠ same residue
- NPC1 c.1554-1009G>A Pathogenic ★★ same type
- NPC1 c.1757+1G>A Likely pathogenic ★★ same type
- NPC1 c.1947+5G>C Pathogenic/Likely pathogenic ★★ same type
- NPC1 c.2130+1G>A Pathogenic ★★ same type
- NPC1 c.2245+1G>A Pathogenic/Likely pathogenic ★★ same type
- NPC1 c.2246-2A>G Pathogenic/Likely pathogenic ★★ same type
- NPC1 c.2515-2A>G Pathogenic/Likely 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-ala885 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown