Is BMP15 p.Leu63Pro (c.188T>C) pathogenic?

BMP15 p.Leu63Pro (c.188T>C) is classified Uncertain significance in BMP15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.0582); Rare (popmax 0.156%, amr); Associated with Inborn genetic diseases.

What condition is associated with BMP15 p.Leu63Pro (c.188T>C)?

BMP15 p.Leu63Pro (c.188T>C) is associated with Inborn genetic diseases (ClinVar).

How common is BMP15 p.Leu63Pro (c.188T>C) in the general population?

BMP15 p.Leu63Pro (c.188T>C) is rare (popmax 0.156%, amr) (gnomAD).

What do computational predictors say about BMP15 p.Leu63Pro (c.188T>C)?

AlphaMissense predicts likely benign (score 0.0582) — an in-silico prediction, not a clinical call.

BMP15 p.Leu63Pro

c.188T>C · VCV3824645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0582 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.156%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0582	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -5.55	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 0.21	GERP -4.1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,820 bp · p 0.097 · regional, not allelic
Overall
CADD	6.683	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 0.156% Admixed American · 67/42,924 alleles

Filtering AF 0.126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.115%

Overall 0.0058% 69/1,190,253 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.156%	641
Remaining individualsnot grpmax-eligible	0.00213%	46,853
African / African-American	0.00176%	56,921

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.Leu63Pro
Coding: c.188T>C
MANE Select: NM_005448
Type: single nucleotide variant
Location: chrX:50910971 (GRCh38)
Structure: AlphaFold pLDDT 72.64

Full BMP15 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

BMP15 p.Leu63Gln Uncertain significance ★ ⚠ same residue
BMP15 p.Ala269Glu Uncertain significance ★ ⚠ same condition
BMP15 p.Arg122Gly Uncertain significance ★ ⚠ same condition
BMP15 p.Arg138Cys Uncertain significance ★ ⚠ same condition
BMP15 p.Arg244Trp Uncertain significance ★ ⚠ same condition
BMP15 p.Arg326Gln Uncertain significance ★ ⚠ same condition
BMP15 p.Arg88Cys Uncertain significance ★ ⚠ same condition
BMP15 p.Arg8Ile 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/bmp15-p-leu63pro (accessed [today's date]).

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