SGCG
Chr 13ARsarcoglycan gamma
Also known as: 35DAG, A4, DAGA4, DMDA, DMDA1, LGMD2C, LGMDR5, MAM
Gamma-sarcoglycan is a sarcolemmal transmembrane glycoprotein that forms part of the dystrophin-glycoprotein complex, providing structural linkage between the muscle fiber cytoskeleton and extracellular matrix. Mutations cause limb-girdle muscular dystrophy type 2C (LGMD2C), an autosomal recessive early-onset muscular dystrophy. The pathogenic mechanism involves loss of protein function leading to sarcolemmal instability and progressive muscle degeneration.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SGCG · 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
External Resources
Links to major genomics databases and tools