The NM_000152.5:c.1082C>G variant in GAA is a missense variant predicted to cause substitution of proline by arginine at amino acid 361 (p.Pro361Arg). At least four individuals with this variant have been reported to have a diagnosis of late-onset Pompe disease (LOPD), with at least two with documented GAA deficiency (PMID: 30312517, 32012848, 42131243) (PP4_Moderate). Of those individuals, three were compound heterozygous for this variant and a pathogenic variant, c.-32-13T>G (PMIDs: 30312517, 32012848) or c.2238C>G (p.Trp746Cys) (PMID: 42131243), phase unknown in all cases. One individual was homozygous for this variant (PMID: 42131243) (PM3_Strong). The highest population minor allele frequency in gnomAD v4.1.1 is 8.475e-7 (1/1179974 alleles) in the European (non-Finnish) population, which is lower than the ClinGen Lysosomal Diseases VCEP’s threshold for PM2_Supporting (<0.001), meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.945 which is above the threshold of 0.7, evidence that correlates with impact to GAA function (PP3). Another missense variant (c.1082C>T (p.Pro361Leu)) (ClinVar Variation ID: 403712) in the same codon has been classified as pathogenic for Pompe disease by the ClinGen Lysosomal Diseases VCEP (PM5). There is a ClinVar entry for this variant (Variation ID: 289367). In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease based on the GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 2.0): PM2_Supporting, PM3_Strong, PM5, PP3, PP4_Moderate. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on July 10, 2026)