COL5A2
Chr 2ADcollagen type V alpha 2 chain
Also known as: EDSC, EDSCL2
The COL5A2 protein forms part of type V collagen, which regulates the assembly of connective tissue fibers containing both type I and type V collagen and is found throughout nearly all tissues. Mutations cause classic Ehlers-Danlos syndrome type 2 with autosomal dominant inheritance, affecting connective tissues and typically presenting in childhood. This gene is extremely intolerant to loss-of-function variants (pLI >0.99, LOEUF 0.097), indicating that most protein-disrupting variants are likely pathogenic.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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.
Literature Evidence
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
COL5A2 · 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