HPS1 p.Phe166=
c.498C>T · rs375340317 · VCV1651055
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00239%, eas)
Conditions
1
Hermansky-Pudlak syndrome 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.181 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.6 | GERP -2.6 |
| Overall | ||
| CADD | 3.204 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00239%
East Asian · 1/41,762 alleles
Filtering AF
0.00141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00119%
Overall
0.00186%
29/1,558,092 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00239% | 41,762 |
| European (non-Finnish) | 0.00209% | 47,949 |
| Admixed American | 0.00193% | 51,780 |
| Finnishnot grpmax-eligible | 0.00167% | 59,756 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,382 |
| South Asian | 0.00118% | 84,478 |
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
- HPS1
- Protein
- p.Phe166=
- Coding
- c.498C>T
- MANE Select
- NM_000195
- dbSNP
- rs375340317
- Type
- single nucleotide variant
- Location
- chr10:98433992 (GRCh38)
- Gene constraint
- LOEUF 0.879 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.44 · 1 PDB
Similar variants
- HPS1 c.1335+1G>A Likely pathogenic ★★ same condition
- HPS1 c.1744-2A>C Pathogenic/Likely pathogenic ★★ same condition
- HPS1 c.1857+1G>A Likely pathogenic ★★ same condition
- HPS1 c.1857+2T>C Pathogenic/Likely pathogenic ★★ same condition
- HPS1 c.1858-1G>A Pathogenic/Likely pathogenic ★★ same condition
- HPS1 c.1940+2T>C Pathogenic/Likely pathogenic ★★ same condition
- HPS1 c.398+2T>C Pathogenic/Likely pathogenic ★★ same condition
- HPS1 c.398+5G>A 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/hps1-p-phe166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown