HS2ST1 p.Pro219=
c.657G>A · rs752107517 · VCV3025006
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00407%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -4.6 |
| Overall | ||
| CADD | 0.074 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00407%
European (non-Finnish) · 48/1,179,930 alleles
Filtering AF
0.00315%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00279%
Overall
0.00328%
53/1,613,902 alleles · very rare
exomes 46/1,461,744 · genomes 7/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00407% | 24,582 |
| Admixed American | 0.00333% | 29,994 |
| East Asian | 0.00223% | 44,882 |
| African / African-American | 0.00133% | 74,924 |
| South Asian | 0.0011% | 91,078 |
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
- HS2ST1
- Protein
- p.Pro219=
- Coding
- c.657G>A
- MANE Select
- NM_012262
- dbSNP
- rs752107517
- Type
- single nucleotide variant
- Location
- chr1:87097906 (GRCh38)
- Gene constraint
- LOEUF 0.683 · pLI 0.23 (gnomAD)
- Structure
- AlphaFold pLDDT 91.89
Similar variants
- HS2ST1 c.364-8C>T Benign ★★ same type
- HS2ST1 p.Arg234= Likely benign ★★ same type
- HS2ST1 p.Ala16Thr Uncertain significance ★ ⚠ same type
- HS2ST1 p.Ala343Ser Uncertain significance ★ ⚠ same type
- HS2ST1 p.Arg123His Uncertain significance ★ ⚠ same type
- HS2ST1 p.Arg188Gln Uncertain significance ★ ⚠ same type
- HS2ST1 p.Arg280His Uncertain significance ★ ⚠ same type
- HS2ST1 p.Arg333Gln 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/hs2st1-p-pro219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown