Is BMP15 p.Arg329Cys (c.985C>T) pathogenic?

BMP15 p.Arg329Cys (c.985C>T) is classified Uncertain significance in BMP15 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-02-07). AlphaMissense: likely benign (0.2661); Ultra-rare (popmax 0.023%, mid); Associated with ovarian dysgenesis 2.

What condition is associated with BMP15 p.Arg329Cys (c.985C>T)?

BMP15 p.Arg329Cys (c.985C>T) is associated with ovarian dysgenesis 2 (ClinVar).

How common is BMP15 p.Arg329Cys (c.985C>T) in the general population?

BMP15 p.Arg329Cys (c.985C>T) is ultra-rare (popmax 0.023%, mid) (gnomAD).

What do computational predictors say about BMP15 p.Arg329Cys (c.985C>T)?

AlphaMissense predicts likely benign (score 0.2661) — an in-silico prediction, not a clinical call.

BMP15 p.Arg329Cys

c.985C>T · rs782375794 · VCV973168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2661 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ovarian dysgenesis 2

Computational evidence

Protein change
AlphaMissense	0.2661	likely benign
REVEL	0.484	indeterminate
SaProt	LLR -9.57	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -0.088
Regional constraint	o/e 1.09	unconstrained · MANE · 5,820 bp · p 0.097 · regional, not allelic
Overall
CADD	19.63	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 0.023% Middle Eastern · 1/4,344 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.000821% 9/1,095,630 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,344
East Asian	0.0119%	8,436
South Asian	0.00353%	28,346
European (non-Finnish)	0.000224%	446,764

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: BMP15
Protein: p.Arg329Cys
Coding: c.985C>T
MANE Select: NM_005448
dbSNP: rs782375794
Type: single nucleotide variant
Location: chrX:50916413 (GRCh38)
Structure: AlphaFold pLDDT 72.64
Residue 329: a disulfide bond; a UniProt-annotated variant site (in pof4)

Full BMP15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ovarian dysgenesis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMP15 p.Arg329His Uncertain significance ★ ⚠ same residue
BMP15 p.Gly271Cys Uncertain significance ★★ ⚠ same condition
BMP15 c.-9C>G Benign ★★ same condition
BMP15 c.*13G>A Benign ★★ same condition
BMP15 p.Asn103Ser Benign ★★ same condition
BMP15 p.Gly54= Benign/Likely benign ★★ same condition
BMP15 p.His337= Benign ★★ same condition
BMP15 p.Leu148Pro Benign/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/bmp15-p-arg329cys (accessed [today's date]).

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