Is BMP2 p.Ala322Asp (c.965C>A) pathogenic?

BMP2 p.Ala322Asp (c.965C>A) is classified Uncertain significance in BMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BMP2 p.Ala322Asp (c.965C>A)?

BMP2 p.Ala322Asp (c.965C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BMP2 p.Ala322Asp (c.965C>A) in the general population?

BMP2 p.Ala322Asp (c.965C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP2 p.Ala322Asp (c.965C>A)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

BMP2 p.Ala322Asp

c.965C>A · VCV4214258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 3% in BMP2
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -16.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	29.2	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.Ala322Asp
Coding: c.965C>A
MANE Select: NM_001200
Type: single nucleotide variant
Location: chr20:6778863 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 322: a UniProt-annotated variant site (in ssfsc1)

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-ala322asp (accessed [today's date]).

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