Is HSD3B2 p.Pro195= (c.585A>G) pathogenic?

HSD3B2 p.Pro195= (c.585A>G) is classified Likely benign in HSD3B2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-27). Very rare (popmax 0.000339%, nfe); Associated with congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency.

How common is HSD3B2 p.Pro195= (c.585A>G) in the general population?

HSD3B2 p.Pro195= (c.585A>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

HSD3B2 p.Pro195=

Q: What condition is associated with HSD3B2 p.Pro195= (c.585A>G)?

HSD3B2 p.Pro195= (c.585A>G) 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.585A>G · rs1378986672 · VCV1628777

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

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

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 -2.1	GERP -3.5
Overall
CADD	0.621	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,990 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,966 alleles · very rare exomes 4/1,461,820 · genomes 1/152,146 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)grpmax	0.000339%	294,997

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: HSD3B2
Protein: p.Pro195=
Coding: c.585A>G
MANE Select: NM_000198
dbSNP: rs1378986672
Type: single nucleotide variant
Location: chr1:119422086 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.30

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 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.Ala82Thr Pathogenic/Likely pathogenic ★★ same condition
HSD3B2 p.Arg249Ter Pathogenic/Likely pathogenic ★★ same condition
HSD3B2 p.Arg335Ter Pathogenic ★★ same condition
HSD3B2 p.Cys5Ter Pathogenic ★★ same condition
HSD3B2 p.Gln311Ter Pathogenic/Likely 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-pro195 (accessed [today's date]).

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