HSD11B2 p.Pro181=
c.543A>G · VCV3650363
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.01%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -5.2 |
| Overall | ||
| CADD | 4.238 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/60,012 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.000434%
7/1,614,084 alleles · very rare
exomes 2/1,461,880 · genomes 5/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 10,002 |
| African / African-American | 0.00133% | 74,928 |
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
- HSD11B2
- Protein
- p.Pro181=
- Coding
- c.543A>G
- MANE Select
- NM_000196
- Type
- single nucleotide variant
- Location
- chr16:67436021 (GRCh38)
- Gene constraint
- LOEUF 1.204 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.49
Similar variants
- HSD11B2 p.Ala328Val Likely pathogenic ★★ same type
- HSD11B2 p.Arg208His Pathogenic/Likely pathogenic ★★ same type
- HSD11B2 c.664+14C>T Uncertain significance ★★ same type
- HSD11B2 c.802+5G>C Uncertain significance ★★ same type
- HSD11B2 p.Ala196Thr Uncertain significance ★★ ⚠ same type
- HSD11B2 p.Ala19Val Uncertain significance ★★ ⚠ same type
- HSD11B2 p.Ala389Thr Uncertain significance ★★ ⚠ same type
- HSD11B2 p.Arg147His 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/hsd11b2-p-pro181 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown