BMPR2 c.*488C>A
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.314%, mid)
Conditions
1
pulmonary hypertension, primary, 1
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 0.18 | GERP 0.2, phastCons 0.94 |
| Non-coding constraint | Z -0.25 | 1 kb window · o/e 1.02 · regional · uncalibrated |
| Overall | ||
| CADD | 7.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.314%
Middle Eastern · 1/318 alleles
Filtering AF
0.169%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.159%
Overall
0.104%
177/170,154 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.314% | 318 |
| European (non-Finnish) | 0.194% | 515 |
| African / African-American | 0.0528% | 1,893 |
| South Asian | 0.0136% | 7,370 |
| Finnishnot grpmax-eligible | 0.00868% | 11,526 |
| Admixed American | 0.00555% | 18,030 |
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
- Coding
- c.*488C>A
- MANE Select
- NM_001204
- dbSNP
- rs574109523
- Type
- single nucleotide variant
- Location
- chr2:202560434 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.07 · 7 PDB
Similar variants
- 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
- BMPR2 c.247+6T>G 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-c-star-488c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown