Is BMP2 p.Ser351Phe (c.1052C>T) pathogenic?

BMP2 p.Ser351Phe (c.1052C>T) is classified Uncertain significance in BMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely pathogenic (0.9763); Absent from gnomAD v4.1.

How common is BMP2 p.Ser351Phe (c.1052C>T) in the general population?

BMP2 p.Ser351Phe (c.1052C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP2 p.Ser351Phe (c.1052C>T)?

AlphaMissense predicts likely pathogenic (score 0.9763) — an in-silico prediction, not a clinical call.

BMP2 p.Ser351Phe

c.1052C>T · VCV3723540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9763	likely pathogenic
REVEL	0.501	indeterminate
SaProt	LLR -12.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: BMP2
Protein: p.Ser351Phe
Coding: c.1052C>T
MANE Select: NM_001200
Type: single nucleotide variant
Location: chr20:6778950 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 351: a disulfide bond; a UniProt-annotated variant site (in ssfsc1); an α-helix

Full BMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP2 p.Ser351Cys Pathogenic same residue
BMP2 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Cys329Ter Likely pathogenic ★★ same type
BMP2 p.Gln89Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Glu229Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Ser92Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Ala103Thr Uncertain significance ★★ ⚠ same type

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-ser351phe (accessed [today's date]).

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