HSD3B7 p.Pro221=
c.663G>A · VCV3619651
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00666%, amr)
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 -2.4 | GERP -4.4 |
| Overall | ||
| CADD | 1.014 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
Admixed American · 4/60,026 alleles
Filtering AF
0.00225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00124%
20/1,612,926 alleles · very rare
exomes 17/1,460,574 · genomes 3/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00666% | 15,006 |
| East Asian | 0.00446% | 22,422 |
| South Asian | 0.00439% | 22,769 |
| European (non-Finnish) | 0.000848% | 117,958 |
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
- HSD3B7
- Protein
- p.Pro221=
- Coding
- c.663G>A
- MANE Select
- NM_025193
- Type
- single nucleotide variant
- Location
- chr16:30986971 (GRCh38)
- Gene constraint
- LOEUF 1.411 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 94.01
Similar variants
- HSD3B7 p.Pro221Leu Uncertain significance ★ ⚠ same residue
- HSD3B7 p.Arg27Ter Pathogenic/Likely pathogenic ★★ same type
- HSD3B7 p.Glu147Lys Pathogenic/Likely pathogenic ★★ same type
- HSD3B7 p.Glu167Ter Pathogenic/Likely pathogenic ★★ same type
- HSD3B7 c.167-6G>A Uncertain significance ★★ same type
- HSD3B7 p.Ala364Thr Uncertain significance ★★ ⚠ same type
- HSD3B7 p.Ala76Thr Uncertain significance ★★ ⚠ same type
- HSD3B7 p.Arg110Gln 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/hsd3b7-p-pro221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown