NPC1 p.Val1044=
c.3132G>A · rs138054593 · VCV1129536
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
Conditions
2
Inborn genetic diseases
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 0.54 | GERP -0.35, phastCons 1 |
| Overall | ||
| CADD | 7.468 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,888 alleles
Filtering AF
0.00676%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00522%
Overall
0.00161%
26/1,614,168 alleles · ultra-rare
exomes 20/1,461,880 · genomes 6/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,481 |
| South Asian | 0.0121% | 8,280 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
| European (non-Finnish) | 0.000593% | 168,575 |
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.Val1044=
- Coding
- c.3132G>A
- MANE Select
- NM_000271
- dbSNP
- rs138054593
- Type
- single nucleotide variant
- Location
- chr18:23536786 (GRCh38)
- Gene constraint
- LOEUF 0.676 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.35 · 20 PDB
Similar variants
- NPC1 p.Val1044Met Uncertain significance ★★ ⚠ 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-val1044 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown