Is BMP2 p.Val352Phe (c.1054G>T) pathogenic?

BMP2 p.Val352Phe (c.1054G>T) is classified Uncertain significance in BMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: ambiguous (0.5397); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BMP2 p.Val352Phe (c.1054G>T)?

BMP2 p.Val352Phe (c.1054G>T) is associated with Inborn genetic diseases (ClinVar).

How common is BMP2 p.Val352Phe (c.1054G>T) in the general population?

BMP2 p.Val352Phe (c.1054G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP2 p.Val352Phe (c.1054G>T)?

AlphaMissense predicts ambiguous (score 0.5397) — an in-silico prediction, not a clinical call.

BMP2 p.Val352Phe

c.1054G>T · rs1986564128 · VCV2557323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5397 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5397	ambiguous
REVEL	0.862	moderately pathogenic-leaning
SaProt	LLR -9.24	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.8, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 288 bp · p 5.3e-06 · regional, not allelic
Overall
CADD	27.8	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

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: BMP2
Protein: p.Val352Phe
Coding: c.1054G>T
MANE Select: NM_001200
dbSNP: rs1986564128
Type: single nucleotide variant
Location: chr20:6778952 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 352: a UniProt-annotated variant site (in ssfsc1); an α-helix

Full BMP2 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

BMP2 p.Arg215Gln Uncertain significance ★★ ⚠ same condition
BMP2 p.Arg291His Uncertain significance ★★ ⚠ same condition
BMP2 p.Arg6Cys Uncertain significance ★★ ⚠ same condition
BMP2 p.Glu234Gly Uncertain significance ★★ ⚠ same condition
BMP2 p.Glu235Asp Uncertain significance ★★ ⚠ same condition
BMP2 p.Gly327Arg Uncertain significance ★★ ⚠ same condition
BMP2 p.His168Asn Uncertain significance ★★ ⚠ same condition
BMP2 p.His221Arg 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/bmp2-p-val352phe (accessed [today's date]).

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