HPS4 p.Ala596=
c.1788C>G · rs770733264 · VCV1617516
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, afr)
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 0.89 | GERP -1.6, phastCons 0.33 |
| Overall | ||
| CADD | 2.243 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,910 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.00031%
5/1,614,006 alleles · very rare
exomes 1/1,461,850 · genomes 4/152,156 · joint denominator
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.Ala596=
- Coding
- c.1788C>G
- MANE Select
- NM_022081
- dbSNP
- rs770733264
- Type
- single nucleotide variant
- Location
- chr22:26458503 (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 type
- HPS4 c.706+1G>A Pathogenic/Likely pathogenic ★★ same type
- HPS4 p.Arg217Ter Pathogenic/Likely pathogenic ★★ same type
- HPS4 p.Gln378Ter Pathogenic/Likely pathogenic ★★ same type
- HPS4 p.Gln50Ter Likely pathogenic ★★ same type
- HPS4 p.Gln516Ter Pathogenic/Likely pathogenic ★★ same type
- HPS4 p.Glu444Ter Pathogenic/Likely pathogenic ★★ same type
- HPS4 c.1846+3A>G Uncertain significance ★★ 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/hps4-p-ala596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown