Is BMP15 p.Val367Phe (c.1099G>T) pathogenic?

BMP15 p.Val367Phe (c.1099G>T) is classified Uncertain significance in BMP15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.2482); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BMP15 p.Val367Phe (c.1099G>T)?

BMP15 p.Val367Phe (c.1099G>T) is associated with Inborn genetic diseases (ClinVar).

How common is BMP15 p.Val367Phe (c.1099G>T) in the general population?

BMP15 p.Val367Phe (c.1099G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP15 p.Val367Phe (c.1099G>T)?

AlphaMissense predicts likely benign (score 0.2482) — an in-silico prediction, not a clinical call.

BMP15 p.Val367Phe

c.1099G>T · VCV3824648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2482 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2482	likely benign
REVEL	0.359	indeterminate
SaProt	LLR -9.10	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 -0.11	GERP -3.7
Regional constraint	o/e 1.09	unconstrained · MANE · 5,820 bp · p 0.097 · regional, not allelic
Overall
CADD	10.16	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMP15
Protein: p.Val367Phe
Coding: c.1099G>T
MANE Select: NM_005448
Type: single nucleotide variant
Location: chrX:50916527 (GRCh38)
Structure: AlphaFold pLDDT 72.64
Residue 367: a disulfide bond

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.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
BMP15 p.Asn197Ile 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-val367phe (accessed [today's date]).

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