HSD17B3 p.Ser232=
c.696G>A · rs375855473 · VCV1989639
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00933%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | |
| Overall | ||
| CADD | 0.013 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00933%
African / African-American · 7/75,026 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00308%
Overall
0.00142%
23/1,614,114 alleles · very rare
exomes 18/1,461,862 · genomes 5/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00933% | 10,718 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| East Asian | 0.00446% | 22,442 |
| South Asian | 0.0022% | 45,532 |
| European (non-Finnish) | 0.000678% | 147,504 |
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
- HSD17B3
- Protein
- p.Ser232=
- Coding
- c.696G>A
- MANE Select
- NM_000197
- dbSNP
- rs375855473
- Type
- single nucleotide variant
- Location
- chr9:96240884 (GRCh38)
- Gene constraint
- LOEUF 0.903 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.59
- Residue 232
- a UniProt-annotated variant site (in mph; almost complete loss of testosterone 17-beta-dehydrogenase (nadp(+)) activity)
Similar variants
- HSD17B3 p.Ser232Leu Pathogenic ★★ same residue
- HSD17B3 c.194C>T Pathogenic/Likely pathogenic ★★ same type
- HSD17B3 c.201+1G>A Pathogenic ★★ same type
- HSD17B3 c.202-1G>A Pathogenic ★★ same type
- HSD17B3 c.277+4A>T Pathogenic ★★ same type
- HSD17B3 c.278-1G>C Pathogenic ★★ same type
- HSD17B3 p.Ala203Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- HSD17B3 p.Arg80Gln 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/hsd17b3-p-ser232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown