Is BMP15 p.Ser5Arg (c.13A>C) pathogenic?

BMP15 p.Ser5Arg (c.13A>C) is classified Benign/Likely benign in BMP15 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2019-05-28). AlphaMissense: likely benign (0.3204); Common (popmax 11.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ovarian dysgenesis 2.

What condition is associated with BMP15 p.Ser5Arg (c.13A>C)?

BMP15 p.Ser5Arg (c.13A>C) is associated with ovarian dysgenesis 2 (ClinVar).

What do computational predictors say about BMP15 p.Ser5Arg (c.13A>C)?

AlphaMissense predicts likely benign (score 0.3204) — an in-silico prediction, not a clinical call.

BMP15 p.Ser5Arg

Q: How common is BMP15 p.Ser5Arg (c.13A>C) in the general population?

BMP15 p.Ser5Arg (c.13A>C) is common (popmax 11.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.13A>C · rs113099187 · VCV259774

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.3204 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.1%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian dysgenesis 2

Computational evidence

Protein change
AlphaMissense	0.3204	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57	GERP 1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,820 bp · p 0.097 · regional, not allelic
Overall
CADD	15.42	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 11.1% African / African-American · 6,332/57,134 alleles

Filtering AF 10.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.8%

Overall 0.596% 7,190/1,205,757 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.1%	9
Remaining individualsnot grpmax-eligible	0.847%	118
Admixed American	0.773%	129
Middle Eastern	0.414%	242
Ashkenazi Jewishnot grpmax-eligible	0.0683%	1,463
South Asian	0.0143%	6,984
European (non-Finnish)	0.00706%	14,170

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.Ser5Arg
Coding: c.13A>C
MANE Select: NM_005448
dbSNP: rs113099187
Type: single nucleotide variant
Location: chrX:50910796 (GRCh38)
Structure: AlphaFold pLDDT 72.64
Residue 5: a UniProt-annotated variant site (no or minor deleterious effect observed)

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.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-ser5arg (accessed [today's date]).

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