Is BMP15 p.Arg68Trp (c.202C>T) pathogenic?

BMP15 p.Arg68Trp (c.202C>T) is classified Conflicting classifications of pathogenicity in BMP15 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.1375); Rare (popmax 0.138%, nfe); Associated with ovarian dysgenesis 2.

What condition is associated with BMP15 p.Arg68Trp (c.202C>T)?

BMP15 p.Arg68Trp (c.202C>T) is associated with ovarian dysgenesis 2, premature ovarian failure 4 (ClinVar).

How common is BMP15 p.Arg68Trp (c.202C>T) in the general population?

BMP15 p.Arg68Trp (c.202C>T) is rare (popmax 0.138%, nfe) (gnomAD).

What do computational predictors say about BMP15 p.Arg68Trp (c.202C>T)?

AlphaMissense predicts likely benign (score 0.1375) — an in-silico prediction, not a clinical call.

BMP15 p.Arg68Trp

c.202C>T · rs104894763 · VCV11474

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1375 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ovarian dysgenesis 2

Computational evidence

Protein change
AlphaMissense	0.1375	likely benign
REVEL	0.478	indeterminate
SaProt	LLR -9.70	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 0.25	GERP -0.97, phastCons 0.006
Regional constraint	o/e 1.09	unconstrained · MANE · 5,820 bp · p 0.097 · regional, not allelic
Overall
CADD	18.42	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.138% European (non-Finnish) · 1,224/884,748 alleles

Filtering AF 0.132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.111% 1,321/1,190,144 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.138%	723
Remaining individualsnot grpmax-eligible	0.111%	901
Admixed American	0.0465%	2,153
Middle Eastern	0.0236%	4,245
African / African-American	0.0229%	4,375
South Asian	0.0185%	5,413
East Asian	0.00307%	32,580

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.Arg68Trp
Coding: c.202C>T
MANE Select: NM_005448
dbSNP: rs104894763
Type: single nucleotide variant
Location: chrX:50910985 (GRCh38)
Structure: AlphaFold pLDDT 72.64
Residue 68: a UniProt-annotated variant site (in pof4; leads to marked reduction of mature protein production; does not generate a complete recovery of wild-type activity in granulosa cell line transfected with defective mutant and with equal amount of wild-type protein)

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

Also linked: premature ovarian failure 4

Similar variants

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
BMP15 p.Phe194Ser 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-arg68trp (accessed [today's date]).

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