RALGPS1
Chr 9Ral GEF with PH domain and SH3 binding motif 1
Also known as: RALGEF2, RALGPS1A
The protein functions as a guanine nucleotide exchange factor for the small GTPase RALA and is involved in cytoskeletal organization. Loss-of-function mutations in RALGPS1 cause autosomal dominant neurodevelopmental disorder, as the gene is highly intolerant to loss-of-function variation (pLI=1.0, LOEUF=0.127). The pathogenic mechanism involves haploinsufficiency affecting Ral protein signal transduction pathways critical for normal neuronal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
164 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 | 1 | 0 | 1 |
VUS | 0 | 109 | 1 | 0 | 110 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 111 | 36 | 0 | 147 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RALGPS1 · 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 →No open access results found
External Resources
Links to major genomics databases and tools