HS2ST1 p.Ala331=
c.993C>T · rs746757317 · VCV2638913
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00879%, sas)
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 -6.6 | GERP -4.3 |
| Overall | ||
| CADD | 2.868 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00879%
South Asian · 8/91,062 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.00248%
40/1,613,444 alleles · very rare
exomes 36/1,461,408 · genomes 4/152,036 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00879% | 11,383 |
| European (non-Finnish) | 0.00271% | 36,862 |
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.Ala331=
- Coding
- c.993C>T
- MANE Select
- NM_012262
- dbSNP
- rs746757317
- Type
- single nucleotide variant
- Location
- chr1:87104618 (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-ala331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown