BMP2 p.Pro363=
c.1089G>A · rs146731183 · VCV742274
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
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 -4.3 | GERP -5.5 |
| Overall | ||
| CADD | 0.611 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,972 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00155%
25/1,613,684 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,993 |
| East Asian | 0.00223% | 44,874 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
| European (non-Finnish) | 0.00153% | 65,554 |
| African / African-American | 0.00134% | 74,804 |
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
- BMP2
- Protein
- p.Pro363=
- Coding
- c.1089G>A
- MANE Select
- NM_001200
- dbSNP
- rs146731183
- Type
- single nucleotide variant
- Location
- chr20:6778987 (GRCh38)
- Gene constraint
- LOEUF 0.213 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.37 · 21 PDB
- Residue 363
- a disulfide bond; a UniProt-annotated variant site (in ssfsc1); a β-strand
Similar variants
- BMP2 p.Pro363Leu Likely pathogenic ★ same residue
- BMP2 p.Pro363Arg Uncertain significance ★ ⚠ same residue
- BMP2 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same type
- BMP2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same type
- BMP2 p.Cys329Ter Likely pathogenic ★★ same type
- BMP2 p.Gln89Ter Pathogenic/Likely pathogenic ★★ same type
- BMP2 p.Glu229Ter Pathogenic/Likely pathogenic ★★ same type
- BMP2 p.Ser92Ter Pathogenic/Likely pathogenic ★★ 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/bmp2-p-pro363 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown