RALGAPA2
Chr 20Ral GTPase activating protein catalytic subunit alpha 2
Also known as: AS250, C20orf74, bA287B20.1, dJ1049G11, dJ1049G11.4, p220
The RALGAPA2 protein serves as the catalytic subunit of the RalGAP2 complex, which activates GTPase activity for the small GTPases RALA and RALB involved in cellular signaling and protein localization. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely pathogenic.
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
369 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 | 22 | 0 | 22 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 1 | 282 | 3 | 0 | 286 |
Likely Benign | 0 | 9 | 0 | 3 | 12 |
Benign | 0 | 1 | 0 | 1 | 2 |
| Total | 1 | 292 | 28 | 4 | 325 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RALGAPA2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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