AGAP1
Chr 2ArfGAP with GTPase domain, ankyrin repeat and PH domain 1
Also known as: AGAP-1, CENTG2, GGAP1, cnt-g2
This gene encodes a GTPase-activating protein that regulates ARF1 and ARF5, and directly controls adapter protein 3 (AP-3)-dependent trafficking of proteins in the endosomal-lysosomal system. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and thin corpus callosum. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.23), indicating that biallelic mutations are required for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
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
404 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 | 56 | 0 | 56 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 1 | 145 | 34 | 0 | 180 |
Likely Benign | 0 | 5 | 44 | 59 | 108 |
Benign | 1 | 3 | 8 | 18 | 30 |
Conflicting | — | 2 | |||
| Total | 2 | 153 | 144 | 77 | 378 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
AGAP1 · 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 →External Resources
Links to major genomics databases and tools