Is BMP1 p.Arg351Pro (c.1052G>C) pathogenic?

BMP1 p.Arg351Pro (c.1052G>C) is classified Uncertain significance in BMP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.9894); Very rare (popmax 0.00195%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BMP1 p.Arg351Pro (c.1052G>C)?

BMP1 p.Arg351Pro (c.1052G>C) is associated with Inborn genetic diseases (ClinVar).

How common is BMP1 p.Arg351Pro (c.1052G>C) in the general population?

BMP1 p.Arg351Pro (c.1052G>C) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about BMP1 p.Arg351Pro (c.1052G>C)?

AlphaMissense predicts likely pathogenic (score 0.9894) — an in-silico prediction, not a clinical call.

BMP1 p.Arg351Pro

c.1052G>C · rs577420762 · VCV1443026

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9894 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9894	likely pathogenic
REVEL	0.519	indeterminate
SaProt	LLR -14.54	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 35 kb · p 1e-07 · regional, not allelic
Overall
CADD	32.0	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 0.00195% European (non-Finnish) · 23/1,179,900 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00143% 23/1,613,718 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: BMP1
Protein: p.Arg351Pro
Coding: c.1052G>C
MANE Select: NM_006129
dbSNP: rs577420762
Type: single nucleotide variant
Location: chr8:22180458 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 351: the cub 1 domain

Full BMP1 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

BMP1 p.Arg351His Uncertain significance ★★ ⚠ same residue
BMP1 p.Arg351Cys Uncertain significance ★ ⚠ same residue
BMP1 p.Arg351= Likely benign ★ same residue
BMP1 p.Ala657Thr Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg395His Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg508His Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg524Cys Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg562Trp 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/bmp1-p-arg351pro (accessed [today's date]).

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