RAPGEF2 p.Pro197=
c.591A>C · rs139146857 · VCV720334
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.6%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -5.4, phastCons 0.99 |
| Overall | ||
| CADD | 6.708 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.6%
African / African-American · 1,199/74,758 alleles
Filtering AF
1.53%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.5%
Overall
0.085%
1,364/1,604,400 alleles · low-frequency
exomes 696/1,452,152 · genomes 668/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.6% | 62 |
| Middle Eastern | 0.165% | 605 |
| Remaining individualsnot grpmax-eligible | 0.119% | 840 |
| Admixed American | 0.0768% | 1,303 |
| European (non-Finnish) | 0.00282% | 35,502 |
| South Asian | 0.0022% | 45,376 |
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
- RAPGEF2
- Protein
- p.Pro197=
- Coding
- c.591A>C
- MANE Select
- NM_001394067
- dbSNP
- rs139146857
- Type
- single nucleotide variant
- Location
- chr4:159304389 (GRCh38)
- Gene constraint
- LOEUF 0.371 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 60.40 · 1 PDB
- Residue 197
- a binding site
Similar variants
- RAPGEF2 p.Arg1333Cys Uncertain significance ★★ ⚠ same type
- RAPGEF2 c.282-12C>A Benign ★★ same type
- RAPGEF2 c.3503-5A>G Benign ★★ same type
- RAPGEF2 c.854-10T>C Benign ★★ same type
- RAPGEF2 p.Ala1219= Likely benign ★★ same type
- RAPGEF2 p.Asn976= Benign ★★ same type
- RAPGEF2 p.Ile536= Benign ★★ same type
- RAPGEF2 p.Pro1641= Benign ★★ same type
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/rapgef2-p-pro197 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown