BMPR2 p.Leu251=
c.753G>A · rs1195908712 · VCV1593113
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00144%, nfe)
Conditions
1
Primary pulmonary hypertension
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 3.7 | GERP 0.84, phastCons 1 |
| Overall | ||
| CADD | 9.576 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00144%
European (non-Finnish) · 17/1,180,052 alleles
Filtering AF
0.000878%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000717%
Overall
0.00105%
17/1,614,216 alleles · very rare
exomes 17/1,461,894 · genomes 0/152,322 · joint denominator
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
- BMPR2
- Protein
- p.Leu251=
- Coding
- c.753G>A
- MANE Select
- NM_001204
- dbSNP
- rs1195908712
- Type
- single nucleotide variant
- Location
- chr2:202518953 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.07 · 7 PDB
- Residue 251
- a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); the protein kinase domain
Similar variants
- BMPR2 c.1128+1G>A Pathogenic ★★ same condition
- BMPR2 c.1128+1G>C Pathogenic ★★ same condition
- BMPR2 c.621+1G>T Pathogenic/Likely pathogenic ★★ same condition
- BMPR2 c.853-2A>G Pathogenic ★★ same condition
- BMPR2 p.Arg147Ter Pathogenic ★★ same condition
- BMPR2 p.Arg213Ter Pathogenic ★★ same condition
- BMPR2 p.Arg491Trp Pathogenic ★★ same condition
- BMPR2 p.Arg873Ter Pathogenic/Likely pathogenic ★★ 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/bmpr2-p-leu251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown