Is HSD3B2 p.Asp74= (c.222C>T) pathogenic?

HSD3B2 p.Asp74= (c.222C>T) is classified Conflicting classifications of pathogenicity in HSD3B2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0659%, nfe); Associated with Inborn genetic diseases.

What condition is associated with HSD3B2 p.Asp74= (c.222C>T)?

HSD3B2 p.Asp74= (c.222C>T) is associated with Inborn genetic diseases, congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency (ClinVar).

How common is HSD3B2 p.Asp74= (c.222C>T) in the general population?

HSD3B2 p.Asp74= (c.222C>T) is ultra-rare (popmax 0.0659%, nfe) (gnomAD).

HSD3B2 p.Asp74=

c.222C>T · rs150892928 · VCV292256

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0659%, nfe)

Conditions

Inborn genetic diseases

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 -3.6	GERP 0.7
Overall
CADD	3.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0659% European (non-Finnish) · 777/1,179,670 alleles

Filtering AF 0.062% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0604%

Overall 0.0519% 837/1,613,532 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0659%	1,518
Admixed American	0.0317%	3,157
Remaining individualsnot grpmax-eligible	0.024%	4,164
East Asian	0.0178%	5,608
African / African-American	0.016%	6,240
Finnishnot grpmax-eligible	0.00469%	21,341
South Asian	0.00329%	30,356

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.Asp74=
Coding: c.222C>T
MANE Select: NM_000198
dbSNP: rs150892928
Type: single nucleotide variant
Location: chr1:119419497 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.30
Residue 74: a UniProt-annotated variant site (in)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency

Similar variants

HSD3B2 p.Asp74Asn Benign/Likely benign ★★ 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-asp74 (accessed [today's date]).

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