Is HSD3B7 p.Ser129= (c.387C>T) pathogenic?

HSD3B7 p.Ser129= (c.387C>T) is classified Likely benign in HSD3B7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-26). Very rare (popmax 0.00801%, afr); Associated with HSD3B7-related disorder.

What condition is associated with HSD3B7 p.Ser129= (c.387C>T)?

HSD3B7 p.Ser129= (c.387C>T) is associated with HSD3B7-related disorder (ClinVar).

How common is HSD3B7 p.Ser129= (c.387C>T) in the general population?

HSD3B7 p.Ser129= (c.387C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

HSD3B7 p.Ser129=

c.387C>T · rs1173248937 · VCV3049549

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

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 2.7	GERP 2.3, phastCons 1
Overall
CADD	18.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,930 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000434% 7/1,614,054 alleles · very rare exomes 4/1,461,834 · genomes 3/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,488
Admixed American	0.00167%	60,012

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.Ser129=
Coding: c.387C>T
MANE Select: NM_025193
dbSNP: rs1173248937
Type: single nucleotide variant
Location: chr16:30986487 (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.Ser129Gly Uncertain significance ★★ ⚠ same residue
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

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-ser129 (accessed [today's date]).

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