HPS1 p.Pro199=
c.597C>T · rs113520308 · VCV167186
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.23%, 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 -6.4 | GERP -2.9 |
| Overall | ||
| CADD | 2.936 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.23%
African / African-American · 923/75,046 alleles
Filtering AF
1.16%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.14%
Overall
0.068%
1,098/1,614,058 alleles · low-frequency
exomes 560/1,461,736 · genomes 538/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.23% | 81 |
| Admixed American | 0.125% | 800 |
| Remaining individualsnot grpmax-eligible | 0.0752% | 1,330 |
| Middle Eastern | 0.066% | 1,515 |
| South Asian | 0.0154% | 6,506 |
| European (non-Finnish) | 0.00297% | 33,715 |
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.Pro199=
- Coding
- c.597C>T
- MANE Select
- NM_000195
- dbSNP
- rs113520308
- Type
- single nucleotide variant
- Location
- chr10:98431202 (GRCh38)
- Gene constraint
- LOEUF 0.879 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.44 · 1 PDB
Similar variants
- HPS1 p.Pro199Leu Uncertain significance ★ ⚠ same residue
- HPS1 p.Pro199fs Likely pathogenic ★ same residue
- HPS1 c.1335+1G>A Likely pathogenic ★★ same type
- HPS1 c.1744-2A>C Pathogenic/Likely pathogenic ★★ same type
- HPS1 c.1857+1G>A Likely pathogenic ★★ same type
- HPS1 c.1857+2T>C Pathogenic/Likely pathogenic ★★ same type
- HPS1 c.1858-1G>A Pathogenic/Likely pathogenic ★★ same type
- HPS1 c.1940+1G>A Pathogenic/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/hps1-p-pro199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown