The NM_000152.5:c.1445C>G variant in GAA is a missense variant predicted to cause substitution of proline by arginine at amino acid 482 (p.Pro482Arg). One proband with this variant was reported to be on enzyme replacement therapy for Pompe disease (PMID: 31392188) (PP4). This proband is compound heterozygous for the variant and a variant classified as pathogenic by the ClinGen LSD VCEP, c.-32-13T>G (PM3_Supporting). This variant is absent in gnomAD v2.1.1. (PM2_Supporting). Expression of the variant in COS7 or HEK293 cells resulted in 0% GAA activity in cells and 0% in medium, and evidence of abnormal synthesis and processing on Western blot, indicating that this variant may impact protein function (PMID 22644586)(PS3_Moderate). The computational predictor REVEL gives a score of 0.948 which is above the threshold of 0.7, evidence that correlates with impact to GAA function (PP3). There is a ClinVar entry for this variant (Variation ID: 1067574; 1 star review status) with one submitter classifying the variant as pathogenic, and two as likely pathogenic. In summary, this variant meets the criteria to be classified as Likely Pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria met, based on the specifications of the ClinGen LSD VCEP (Specifications Version 2.0): PS3_Moderate, PP3, PP4, PM2_Supporting, PM3_Supporting. (Classification approved by the ClinGen LSD VCEP, December 6, 2022).