Is BMP15 p.Thr239Ile (c.716C>T) pathogenic?

BMP15 p.Thr239Ile (c.716C>T) is classified Uncertain significance in BMP15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). AlphaMissense: ambiguous (0.3607); Very rare (popmax 0.00335%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BMP15 p.Thr239Ile (c.716C>T)?

BMP15 p.Thr239Ile (c.716C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BMP15 p.Thr239Ile (c.716C>T) in the general population?

BMP15 p.Thr239Ile (c.716C>T) is very rare (popmax 0.00335%, nfe) (gnomAD).

What do computational predictors say about BMP15 p.Thr239Ile (c.716C>T)?

AlphaMissense predicts ambiguous (score 0.3607) — an in-silico prediction, not a clinical call.

BMP15 p.Thr239Ile

c.716C>T · VCV4214256

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00335%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3607	ambiguous
REVEL	0.456	indeterminate
SaProt	LLR -8.02	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.74, phastCons 0.99
Regional constraint	o/e 1.09	unconstrained · MANE · 5,820 bp · p 0.097 · regional, not allelic
Overall
CADD	17.27	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 0.00335% European (non-Finnish) · 30/895,501 alleles

Filtering AF 0.00238% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.00273% 30/1,098,208 alleles · very rare

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.Thr239Ile
Coding: c.716C>T
MANE Select: NM_005448
Type: single nucleotide variant
Location: chrX:50916144 (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.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-thr239ile (accessed [today's date]).

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