RAPGEF1
Chr 9Rap guanine nucleotide exchange factor 1
Also known as: C3G, GRF2
This gene encodes a guanine nucleotide exchange factor that transduces signals from CRK to activate RAS family GTPases and is essential for nerve growth factor-induced neurite outgrowth, cell adhesion, and endothelial barrier function. The extremely high pLI score (1.0) and low LOEUF score (0.222) indicate the gene is highly intolerant to loss-of-function mutations, suggesting pathogenic variants would likely cause autosomal dominant disease. However, specific neurogenetic disorders caused by RAPGEF1 mutations have not yet been clinically characterized.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
ClinVar Variant Classifications
199 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 34 | 0 | 34 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 115 | 10 | 0 | 125 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 0 | 1 | 2 | 3 |
| Total | 0 | 118 | 47 | 2 | 167 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RAPGEF1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools