Is HSD3B7 p.Pro141= (c.423C>A) pathogenic?

HSD3B7 p.Pro141= (c.423C>A) is classified Likely benign in HSD3B7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-04). Ultra-rare (popmax 0.0467%, amr); Associated with HSD3B7-related disorder.

What condition is associated with HSD3B7 p.Pro141= (c.423C>A)?

HSD3B7 p.Pro141= (c.423C>A) is associated with HSD3B7-related disorder (ClinVar).

How common is HSD3B7 p.Pro141= (c.423C>A) in the general population?

HSD3B7 p.Pro141= (c.423C>A) is ultra-rare (popmax 0.0467%, amr) (gnomAD).

HSD3B7 p.Pro141=

c.423C>A · rs199732996 · VCV3029630

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, amr)

Conditions

HSD3B7-related disorder

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 -0.37	GERP -1.2, phastCons 0.074
Overall
CADD	14.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0467% Admixed American · 28/60,002 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.00273% 44/1,613,680 alleles · ultra-rare exomes 24/1,461,460 · genomes 20/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0467%	2,143
South Asian	0.00439%	22,770
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000932%	107,243

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: HSD3B7
Protein: p.Pro141=
Coding: c.423C>A
MANE Select: NM_025193
dbSNP: rs199732996
Type: single nucleotide variant
Location: chr16:30986523 (GRCh38)
Gene constraint: LOEUF 1.411 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.01

Full HSD3B7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

HSD3B7-related disorder

Similar variants

HSD3B7 p.His155Leu Uncertain significance ⚠ same condition
HSD3B7 p.Ile194Val Uncertain significance same condition
HSD3B7 p.Thr137Ile Uncertain significance ⚠ same condition
HSD3B7 c.432-3C>T Likely benign same condition
HSD3B7 c.531+9A>C Likely benign same condition
HSD3B7 c.*2G>A Likely benign same condition
HSD3B7 p.Ala2= Likely benign same condition
HSD3B7 p.Ala62= Likely benign 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/hsd3b7-p-pro141 (accessed [today's date]).

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