Is BMP3 p.Ala470Pro (c.1408G>C) pathogenic?

BMP3 p.Ala470Pro (c.1408G>C) is classified Uncertain significance in BMP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-11-04). AlphaMissense: likely pathogenic (0.9871); Very rare (popmax 8.86e-05%, nfe).

How common is BMP3 p.Ala470Pro (c.1408G>C) in the general population?

BMP3 p.Ala470Pro (c.1408G>C) is very rare (popmax 8.86e-05%, nfe) (gnomAD).

What do computational predictors say about BMP3 p.Ala470Pro (c.1408G>C)?

AlphaMissense predicts likely pathogenic (score 0.9871) — an in-silico prediction, not a clinical call.

BMP3 p.Ala470Pro

c.1408G>C · VCV3370520

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9871 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.86e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9871	likely pathogenic · top 4% in BMP3
REVEL	0.765	pathogenic-leaning
SaProt	LLR -14.51	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 22 kb · p 0.044 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 8.86e-05% European (non-Finnish) · 1/1,128,754 alleles

Overall 7.37e-05% 1/1,356,988 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: BMP3
Protein: p.Ala470Pro
Coding: c.1408G>C
MANE Select: NM_001201
Type: single nucleotide variant
Location: chr4:81053525 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.11 · 1 PDB
Residue 470: a disulfide bond; a β-strand

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

Similar variants

BMP3 p.Ala470Thr Uncertain significance ★ ⚠ same residue
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

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-ala470pro (accessed [today's date]).

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