BMP2 p.His221=
c.663C>T · rs757394512 · VCV1617935
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00988%, sas)
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 -6.6 | GERP -5.5 |
| Overall | ||
| CADD | 3.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00988%
South Asian · 9/91,078 alleles
Filtering AF
0.00514%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00375%
Overall
0.00254%
41/1,614,134 alleles · very rare
exomes 39/1,461,870 · genomes 2/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00988% | 10,120 |
| Admixed American | 0.00666% | 15,004 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,627 |
| African / African-American | 0.004% | 25,013 |
| East Asian | 0.00223% | 44,872 |
| European (non-Finnish) | 0.00169% | 59,001 |
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.His221=
- Coding
- c.663C>T
- MANE Select
- NM_001200
- dbSNP
- rs757394512
- Type
- single nucleotide variant
- Location
- chr20:6778561 (GRCh38)
- Gene constraint
- LOEUF 0.213 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.37 · 21 PDB
- Residue 221
- a UniProt-annotated variant site (in ssfsc1)
Similar variants
- BMP2 p.His221Arg 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
- BMP2 p.Ala103Thr 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/bmp2-p-his221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown