BMPR2 p.Glu581fs
c.1741del · VCV4959458
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
BMPR2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 12 of 13 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 2.9 | GERP -0.23, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- BMPR2
- Protein
- p.Glu581fs
- Coding
- c.1741del
- MANE Select
- NM_001204
- Type
- Deletion
- Location
- chr2:202555403 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.07 · 7 PDB
- Residue 581
- a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); a UniProt-annotated variant site (in pph1; loss of localization to the plasma membrane; localized to the cytoplasm)
Disease context
BMPR2-related disorder
Similar variants
- BMPR2 p.Lys230fs Pathogenic ★★ same condition
- BMPR2 p.Thr493fs Pathogenic/Likely pathogenic ★★ same condition
- BMPR2 p.Leu319fs Likely pathogenic ★ same condition
- BMPR2 p.Leu745fs Likely pathogenic ★ same condition
- BMPR2 p.Pro653fs Pathogenic ★ same condition
- BMPR2 p.Trp9fs Pathogenic ★ same condition
- BMPR2 p.Glu581Gly Conflicting classifications of pathogenicity ★ same residue
- BMPR2 p.Glu581= Likely benign ★ same residue
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-glu581fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown