Is HSD3B2 p.Pro155= (c.465G>A) pathogenic?

HSD3B2 p.Pro155= (c.465G>A) is classified Conflicting classifications of pathogenicity in HSD3B2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). Rare (popmax 0.161%, sas); Associated with congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency.

How common is HSD3B2 p.Pro155= (c.465G>A) in the general population?

HSD3B2 p.Pro155= (c.465G>A) is rare (popmax 0.161%, sas) (gnomAD).

HSD3B2 p.Pro155=

Q: What condition is associated with HSD3B2 p.Pro155= (c.465G>A)?

HSD3B2 p.Pro155= (c.465G>A) 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.465G>A · rs114527791 · VCV715626

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.161%, sas)

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 -3.8	GERP -3.5
Overall
CADD	0.822	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.161% South Asian · 146/90,736 alleles

Filtering AF 0.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.0505% 815/1,613,670 alleles · rare exomes 698/1,461,464 · genomes 117/152,206 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.294%	341
South Asiangrpmax	0.161%	621
East Asian	0.161%	623
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Middle Eastern	0.033%	3,030
European (non-Finnish)	0.0305%	3,278
African / African-American	0.016%	6,250
Admixed American	0.00833%	12,001
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

Finnish 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.Pro155=
Coding: c.465G>A
MANE Select: NM_000198
dbSNP: rs114527791
Type: single nucleotide variant
Location: chr1:119421966 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.30
Residue 155: a UniProt-annotated variant site (in ah2; nonsalt-wasting form)

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.Pro155Leu Likely pathogenic ★ 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.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

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-pro155 (accessed [today's date]).

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