This variant, c.2152G>A (p.Val718Ile), has a highest continental population minor allele frequency in gnomAD v2.1.1 of 0.00011 in the South Asian population, meeting PM2. When expressed in COS-7 cells, this variant results in 127% GAA activity, and the protein is normally synthesized and/or processed (PMID 22644586), meeting the ClinGen LSD VCEP’s specifications for BS3. However, the finding of normal activity in in vitro assays might not truly reflect the biological activity in vivo. The score for the REVEL in silico predictor is 0.193, meeting BP4. The variant has been reported in an individual with either suspected Pompe disease or a known carrier, but further details are not available (PMID 22644586). There is a ClinVar entry for this variant (Variation ID: 281232, 1 star review status) with 3 submitters classifying the variant as likely benign and 3 submitters classifying the variant as uncertain significance. In summary, this variant meets the criteria to be classified as variant of uncertain significance for Pompe disease. ACMG/AMP criteria met, based on the specification of the ClinGen LSD VCEP: PM2, BS3, BP4.