HPS5 p.Ser265=
c.795G>A · rs371331168 · VCV758558
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -5.8 |
| Overall | ||
| CADD | 0.193 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,884 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.00496%
80/1,613,474 alleles · ultra-rare
exomes 70/1,461,332 · genomes 10/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,481 |
| African / African-American | 0.00935% | 10,699 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,614 |
| European (non-Finnish) | 0.00526% | 19,025 |
| South Asian | 0.0011% | 91,074 |
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
- HPS5
- Protein
- p.Ser265=
- Coding
- c.795G>A
- MANE Select
- NM_181507
- dbSNP
- rs371331168
- Type
- single nucleotide variant
- Location
- chr11:18306164 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.21
Similar variants
- HPS5 p.Ser265Leu Uncertain significance ★ ⚠ same residue
- HPS5 c.1164+1G>A Likely pathogenic ★★ same type
- HPS5 c.1862+1G>A Likely pathogenic ★★ same type
- HPS5 c.220-1G>T Pathogenic ★★ same type
- HPS5 c.2718-2A>G Pathogenic/Likely pathogenic ★★ same type
- HPS5 c.2837+1G>A Likely pathogenic ★★ same type
- HPS5 c.2952-1G>C Likely pathogenic ★★ same type
- HPS5 c.478-2A>G 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/hps5-p-ser265 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown