The NM_000231.3: c.525del p.(Phe175LeufsTer20) variant in SGCG is a frameshift variant that is predicted to introduce a premature stop codon and nonsense mediated decay in a gene for which loss of function is a known mechanism of disease. However, use of an N-terminal antibody in patient muscle tissue suggested that a truncated protein may be produced (PMID: 10942431) (PVS1_Strong). This variant has been detected in at least five apparently unrelated patients with autosomal recessive limb girdle muscular dystrophy, including in a homozygous state in at least four individuals (1.0 pt, PMID: 16616845, 10993494, 18285821, 10942431; ClinVar SCV001164546.1) (PM3). At least one patient with this variant displayed progressive limb girdle muscle weakness (PP4). While absent gamma-sarcoglycan protein expression has been reported in the skeletal muscle of patients with this variant, detection may be dependent on the antibody used (PMID: 10993494, 16616845, 10942431). The variant has been reported to segregate with autosomal recessive LGMD in four affected family members from two families (PP1_Strong; PMID: 10942431, ClinVar SCV001164546.1). The highest population allele frequency of this variant is 0.0001166 in gnomAD v4.1.10 (7/60018 Admixed American chromosomes), which is greater than the ClinGen LGMD threshold (0.00009) for PM2_Supporting (criterion not met). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 2.0.0; 12/23/2025): PVS1_Strong, PM3, PP4, PP1_Strong.