Is BMP3 p.Arg232Lys (c.695G>A) pathogenic?

BMP3 p.Arg232Lys (c.695G>A) is classified Uncertain significance in BMP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.0812); Very rare (popmax 0.005%, amr).

How common is BMP3 p.Arg232Lys (c.695G>A) in the general population?

BMP3 p.Arg232Lys (c.695G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about BMP3 p.Arg232Lys (c.695G>A)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

BMP3 p.Arg232Lys

c.695G>A · rs750935828 · VCV2229487

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.34	GERP -1.2
Regional constraint	o/e 1.08	unconstrained · MANE · 22 kb · p 0.044 · regional, not allelic
Overall
CADD	8.601	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

Grpmax group 0.005% Admixed American · 3/59,976 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000682% 11/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,992
East Asian	0.00223%	44,898
European (non-Finnish)	0.000593%	168,575

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: BMP3
Protein: p.Arg232Lys
Coding: c.695G>A
MANE Select: NM_001201
dbSNP: rs750935828
Type: single nucleotide variant
Location: chr4:81046116 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.11 · 1 PDB

Full BMP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP3 p.Gln176Lys Benign/Likely benign ★★ same type
BMP3 p.Lys345Asn Benign ★★ same type
BMP3 p.Thr222Met Benign ★★ ⚠ same type
BMP3 p.Ala156Val Uncertain significance ★ ⚠ same type
BMP3 p.Ala188Pro Uncertain significance ★ ⚠ same type
BMP3 p.Ala209Val Uncertain significance ★ ⚠ same type
BMP3 p.Ala20Glu Uncertain significance ★ ⚠ same type
BMP3 p.Ala248Ser 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/bmp3-p-arg232lys (accessed [today's date]).

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