BMPR2 p.Arg983Gln
c.2948G>A · rs148099152 · VCV333652
ClinGen expert panel — Pulmonary Hypertension VCEP
Likely Benign for pulmonary arterial hypertension. Applied ACMG criteria (verbatim):
BS1
Curation rationale (ClinGen, verbatim)
The NM_001204.7(BMPR2):c.2948G>A variant is a missense variant predicted to cause substitution of arginine to glutamine at amino acid position 983 (p.Arg983Gln). The highest population minor allele frequency in gnomAD v2.1.1 controls is 0.0034 (8/2358) in the Ashkenazi Jew population, which is higher than the ClinGen PH VCEP threshold (>0.1%) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.4, which is neither above nor below the thresholds predicting a damaging or benign impact on BMPR2 function. In summary, this variant meets the criteria to be classified as likely benign for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: BS1. (VCEP specifications version 1.1, 1/18/2024)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3205 | likely benign |
|---|---|---|
| REVEL | 0.401 | indeterminate |
| SaProt | LLR -7.00 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.4, phastCons 1 |
| Regional constraint | o/e 0.80 | unconstrained · MANE · 169 bp · p 0.093 · regional, not allelic |
| Overall | ||
| CADD | 24.8 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.598% | 167 |
| Middle Easterngrpmax | 0.0495% | 2,021 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| Admixed American | 0.0183% | 5,455 |
| European (non-Finnish) | 0.00924% | 10,826 |
| South Asian | 0.00329% | 30,358 |
| Finnishnot grpmax-eligible | 0.00156% | 64,020 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg983Gln
- Coding
- c.2948G>A
- MANE Select
- NM_001204
- dbSNP
- rs148099152
- Type
- single nucleotide variant
- Location
- chr2:202559777 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.07 · 7 PDB
- Residue 983
- 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: mitral valve prolapsepulmonary 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.Arg983Leu Uncertain significance ★ ⚠ same residue
- BMPR2 p.Arg983Trp 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
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-arg983gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown