ALS2CL
Chr 3ALS2 C-terminal like
Also known as: RN49018
The protein acts as a guanine nucleotide exchange factor for Rab5 GTPase and regulates endosome dynamics. Mutations cause autosomal recessive spastic paraplegia, with the gene showing low constraint to loss-of-function variation. The condition primarily affects the motor system through progressive spasticity of the lower limbs.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
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
194 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 | 7 | 0 | 7 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 1 | 145 | 2 | 0 | 148 |
Likely Benign | 0 | 9 | 0 | 0 | 9 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 1 | 154 | 10 | 0 | 165 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ALS2CL · 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