AGFG1
Chr 2ArfGAP with FG repeats 1
Also known as: HRB, RAB, RIP
The protein encoded by AGFG1 is required for vesicle docking or fusion during acrosome biogenesis and plays a role in RNA trafficking from the nucleus to cytoplasm. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in infancy with seizures and severe developmental delays. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.
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
108 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 | 1 | 0 | 1 |
VUS | 0 | 46 | 4 | 0 | 50 |
Likely Benign | 0 | 4 | 0 | 3 | 7 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 50 | 27 | 3 | 80 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
AGFG1 · 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