Is BMP1 p.Arg682= (c.2046C>T) pathogenic?

BMP1 p.Arg682= (c.2046C>T) is classified Likely benign in BMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). Ultra-rare (popmax 0.0374%, afr).

How common is BMP1 p.Arg682= (c.2046C>T) in the general population?

BMP1 p.Arg682= (c.2046C>T) is ultra-rare (popmax 0.0374%, afr) (gnomAD).

BMP1 p.Arg682=

c.2046C>T · rs369306746 · VCV2072099

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0374%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -5.4
Overall
CADD	1.375	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0374% African / African-American · 28/74,896 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.00223% 36/1,613,784 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0374%	2,675
Middle Eastern	0.0164%	6,080
East Asian	0.00446%	22,442
Remaining individualsnot grpmax-eligible	0.0032%	31,238
European (non-Finnish)	0.000254%	393,280

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.Arg682=
Coding: c.2046C>T
MANE Select: NM_006129
dbSNP: rs369306746
Type: single nucleotide variant
Location: chr8:22197359 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 682: the cub 3 domain

Full BMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP1 p.Arg682His Uncertain significance ★ ⚠ same residue
BMP1 p.Cys183Ter Pathogenic/Likely pathogenic ★★ same type
BMP1 p.Gln70Ter Pathogenic/Likely pathogenic ★★ same type
BMP1 c.1443+6T>C Uncertain significance ★★ same type
BMP1 c.1639+4C>G Uncertain significance ★★ same type
BMP1 c.2233+4C>T Uncertain significance ★★ same type
BMP1 c.*452A>C Uncertain significance ★★ same type
BMP1 p.Ala538Val 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/bmp1-p-arg682 (accessed [today's date]).

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