BMPR2 p.Ile566=
c.1698T>A · rs948158717 · VCV898486
ClinGen expert panel — Pulmonary Hypertension VCEP
Uncertain Significance for pulmonary arterial hypertension. Applied ACMG criteria (verbatim):
PM2_Supporting BP7 BP4
Curation rationale (ClinGen, verbatim)
The NM_001204.7(BMPR2) c.1698T>A variant is a synonymous (silent) variant (p.Ile566=) that is not predicted by SpliceAI to impact splicing (BP4, BP7). This variant is absent from gnomAD v2.1.1 controls (PM2_supporting). Due to conflicting evidence, this variant is classified as a variant of uncertain significance for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BP4, BP7, PM2_supporting. (VCEP specifications version 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. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -0.2, phastCons 1 |
| Overall | ||
| CADD | 7.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00695% | 14,391 |
| African / African-American | 0.00267% | 37,457 |
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.Ile566=
- Coding
- c.1698T>A
- MANE Select
- NM_001204
- dbSNP
- rs948158717
- Type
- single nucleotide variant
- Location
- chr2:202555363 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.07 · 7 PDB
- Residue 566
- 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
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.Ile566Ser Uncertain significance ★ ⚠ same residue
- BMPR2 c.1276+3A>G Likely pathogenic ★★★ same condition
- BMPR2 c.1276+3A>T Likely pathogenic ★★★ same condition
- BMPR2 c.1276+4A>G Likely pathogenic ★★★ same condition
- BMPR2 c.1277-8A>G Pathogenic ★★★ same condition
- BMPR2 c.1277-9A>G Pathogenic ★★★ same condition
- BMPR2 c.1413+1G>A Pathogenic ★★★ same condition
- BMPR2 c.247+1G>A 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-ile566 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown