HPS4 p.Ser693=
c.2079C>T · rs138189133 · VCV211152
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.35%, sas)
Conditions
1
Hermansky-Pudlak syndrome 4
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 -15 | GERP -3.1 |
| Overall | ||
| CADD | 0.204 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.35%
South Asian · 3,049/91,082 alleles
Filtering AF
3.25%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.21%
Overall
0.201%
3,242/1,614,206 alleles · low-frequency
exomes 3,083/1,461,884 · genomes 159/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 3.35% | 30 |
| Remaining individualsnot grpmax-eligible | 0.224% | 446 |
| Middle Eastern | 0.181% | 551 |
| East Asian | 0.0156% | 6,412 |
| African / African-American | 0.004% | 25,018 |
| European (non-Finnish) | 0.00263% | 38,066 |
| Admixed American | 0.00167% | 60,028 |
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
- HPS4
- Protein
- p.Ser693=
- Coding
- c.2079C>T
- MANE Select
- NM_022081
- dbSNP
- rs138189133
- Type
- single nucleotide variant
- Location
- chr22:26453281 (GRCh38)
- Gene constraint
- LOEUF 0.794 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.83 · 1 PDB
Similar variants
- HPS4 c.133-2A>G Likely pathogenic ★★ same condition
- HPS4 c.706+1G>A Pathogenic/Likely pathogenic ★★ same condition
- HPS4 p.Arg217Ter Pathogenic/Likely pathogenic ★★ same condition
- HPS4 p.Gln378Ter Pathogenic/Likely pathogenic ★★ same condition
- HPS4 p.Gln50Ter Likely pathogenic ★★ same condition
- HPS4 p.Gln516Ter Pathogenic/Likely pathogenic ★★ same condition
- HPS4 p.Glu444Ter Pathogenic/Likely pathogenic ★★ same condition
- HPS4 c.*1227T>C Uncertain significance ★★ 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/hps4-p-ser693 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown