Is HSD3B2 p.Ala82Pro (c.244G>C) pathogenic?

HSD3B2 p.Ala82Pro (c.244G>C) is classified Likely pathogenic in HSD3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely pathogenic (0.8759); Absent from gnomAD v4.1; Associated with congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency.

How common is HSD3B2 p.Ala82Pro (c.244G>C) in the general population?

HSD3B2 p.Ala82Pro (c.244G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HSD3B2 p.Ala82Pro (c.244G>C)?

AlphaMissense predicts likely pathogenic (score 0.8759) — an in-silico prediction, not a clinical call.

HSD3B2 p.Ala82Pro

Q: What condition is associated with HSD3B2 p.Ala82Pro (c.244G>C)?

HSD3B2 p.Ala82Pro (c.244G>C) is associated with congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency (ClinVar).

Q: How is Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.244G>C · VCV4881970

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8759 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.8759	likely pathogenic ✓ concordant with ClinVar · top 6% in HSD3B2
REVEL	0.949	strongly pathogenic-leaning
SaProt	LLR -11.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,197 bp · p 0.07 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HSD3B2
Protein: p.Ala82Pro
Coding: c.244G>C
MANE Select: NM_000198
Type: single nucleotide variant
Location: chr1:119419519 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.30
Residue 82: a UniProt-annotated variant site (in ah2)

Full HSD3B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

HSD3B2 p.Ala82Thr Pathogenic/Likely pathogenic ★★ same residue
HSD3B2 p.Ala82= Likely benign ★★ same residue
HSD3B2 p.Ala82Val Uncertain significance ★ ⚠ same residue
HSD3B2 c.308-1G>A Likely pathogenic ★★ same condition
HSD3B2 c.308-1G>C Likely pathogenic ★★ same condition
HSD3B2 c.308-6G>A Likely pathogenic ★★ same condition
HSD3B2 p.Arg249Ter Pathogenic/Likely pathogenic ★★ same condition
HSD3B2 p.Arg335Ter Pathogenic ★★ same condition

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/hsd3b2-p-ala82pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown