Is HSD3B2 p.Asp86= (c.258T>C) pathogenic?

HSD3B2 p.Asp86= (c.258T>C) is classified Likely benign in HSD3B2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). Ultra-rare (popmax 0.016%, afr); Associated with congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency.

How common is HSD3B2 p.Asp86= (c.258T>C) in the general population?

HSD3B2 p.Asp86= (c.258T>C) is ultra-rare (popmax 0.016%, afr) (gnomAD).

HSD3B2 p.Asp86=

Q: What condition is associated with HSD3B2 p.Asp86= (c.258T>C)?

HSD3B2 p.Asp86= (c.258T>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.258T>C · rs996323669 · VCV1160815

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -3.4
Overall
CADD	0.157	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,908 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000806% 13/1,613,784 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,242
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Asp86=
Coding: c.258T>C
MANE Select: NM_000198
dbSNP: rs996323669
Type: single nucleotide variant
Location: chr1:119419533 (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-asp86 (accessed [today's date]).

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