RAPGEF2 p.Arg702=
c.2106G>C · VCV3778278
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00602%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.048 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.58 | GERP -4.3, phastCons 0.001 |
| Overall | ||
| CADD | 6.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00602%
European (non-Finnish) · 71/1,180,012 alleles
Filtering AF
0.00486%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00447%
Overall
0.00477%
77/1,614,006 alleles · very rare
exomes 72/1,461,808 · genomes 5/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00602% | 16,620 |
| Finnishnot grpmax-eligible | 0.00469% | 21,340 |
| East Asian | 0.00223% | 44,884 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| African / African-American | 0.00133% | 74,922 |
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.Arg702=
- Coding
- c.2106G>C
- MANE Select
- NM_001394067
- Type
- single nucleotide variant
- Location
- chr4:159332668 (GRCh38)
- Gene constraint
- LOEUF 0.371 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 60.40 · 1 PDB
Similar variants
- RAPGEF2 p.Arg702Gln Uncertain significance ★ ⚠ same residue
- 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
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-arg702 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown