BMPR2 p.Lys81Ter
c.240_241insT · rs1085307183 · VCV425725
ClinGen expert panel — Pulmonary Hypertension VCEP
Likely Pathogenic for pulmonary arterial hypertension. Applied ACMG criteria (verbatim):
PVS1 PM2_Supporting
Curation rationale (ClinGen, verbatim)
The NM_001204.7(BMPR2):c.240_241insT (p.Lys81Ter) variant is a DNA single thymine base insertion predicted to cause a frameshift, replacing a lysine residue for a stop codon at position 81. The variant is absent from the gnomAD v.2.1.1 controls and v3.0 (PM2_supporting). c.240_241insT was found in a patient with pulmonary arterial hypertension (PMID:20496075). The variant resides in the second exon of BMPR2 and generates a stop codon that is predicted to cause nonsense-mediated decay (PVS1). In summary, this variant meets the criteria to be classified as likely pathogenic for pulmonary arterial hypertension based on ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: PM2_supporting, PVS1 (VCEP specification version v 1.1, 1/18/2024).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 13 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP -0.86, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- BMPR2
- Protein
- p.Lys81Ter
- Coding
- c.240_241insT
- MANE Select
- NM_001204
- dbSNP
- rs1085307183
- Type
- Insertion
- Location
- chr2:202464972 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.07 · 7 PDB
- Residue 81
- a disulfide bond; a β-strand
Disease context
pulmonary arterial hypertension — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: pulmonary hypertension, primary, 1
For Idiopathic/heritable pulmonary arterial hypertension (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive, Not applicable
- Onset
- All ages
- Prevalence
- 1-9 / 1 000 000 (United States)
Similar variants
- BMPR2 p.Asp885fs Likely pathogenic ★ same condition
- BMPR2 p.Ile507fs Pathogenic ★ same condition
- BMPR2 p.Thr104fs Likely pathogenic ★ same condition
- BMPR2 p.Val429fs Likely pathogenic ★ same condition
- BMPR2 c.1277-10_1277-9insGGG Pathogenic same condition
- BMPR2 c.852_852+1insA Pathogenic same condition
- BMPR2 p.Arg114fs Pathogenic same condition
- BMPR2 p.Arg32fs 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-lys81ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown