Is HSD3B7 p.Arg287Cys (c.859C>T) pathogenic?

HSD3B7 p.Arg287Cys (c.859C>T) is classified Uncertain significance in HSD3B7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-26). AlphaMissense: likely benign (0.1595); Ultra-rare (popmax 0.0167%, amr); Associated with Inborn genetic diseases.

What condition is associated with HSD3B7 p.Arg287Cys (c.859C>T)?

HSD3B7 p.Arg287Cys (c.859C>T) is associated with Inborn genetic diseases (ClinVar).

How common is HSD3B7 p.Arg287Cys (c.859C>T) in the general population?

HSD3B7 p.Arg287Cys (c.859C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about HSD3B7 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely benign (score 0.1595) — an in-silico prediction, not a clinical call.

HSD3B7 p.Arg287Cys

c.859C>T · rs376499076 · VCV596598

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1595 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1595	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -9.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.86, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,521 bp · p 0.00046 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,028 alleles

Filtering AF 0.00899% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00384% 62/1,613,346 alleles · ultra-rare exomes 54/1,461,022 · genomes 8/152,324 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,003
South Asian	0.00878%	11,386
Remaining individualsnot grpmax-eligible	0.0048%	20,832
African / African-American	0.004%	25,013
European (non-Finnish)	0.00322%	31,053

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.Arg287Cys
Coding: c.859C>T
MANE Select: NM_025193
dbSNP: rs376499076
Type: single nucleotide variant
Location: chr16:30987932 (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

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

Similar variants

HSD3B7 p.Arg203Lys Uncertain significance ★★ ⚠ same condition
HSD3B7 p.Arg243Trp Uncertain significance ★★ ⚠ same condition
HSD3B7 p.Arg27Gln Uncertain significance ★★ ⚠ same condition
HSD3B7 p.Arg32Trp Uncertain significance ★★ ⚠ same condition
HSD3B7 p.Arg354Gln Uncertain significance ★★ ⚠ same condition
HSD3B7 p.Arg35Trp Uncertain significance ★★ ⚠ same condition
HSD3B7 p.Asp43Glu Uncertain significance ★★ ⚠ same condition
HSD3B7 p.Glu152Lys Uncertain significance ★★ ⚠ 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-arg287cys (accessed [today's date]).

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