BMP1 p.Arg227=
c.681G>A · rs1044950527 · VCV2998940
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, 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 3.8 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 11.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,860 alleles
Filtering AF
0.000554%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000137%
2/1,459,702 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.Arg227=
- Coding
- c.681G>A
- MANE Select
- NM_006129
- dbSNP
- rs1044950527
- Type
- single nucleotide variant
- Location
- chr8:22177090 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89 · 8 PDB
- Residue 227
- a disulfide bond; the peptidase m12a domain
Similar variants
- 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
- BMP1 p.Ala657Thr 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-arg227 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown