This variant, c.1826dup (p.Tyr609Terfs), is predicted to cause a frameshift, premature termination codon, and nonsense mediated decay resulting in lack of gene product. This is supported by the absence of cross-reactive immunological material in cultured fibroblasts from a patient with the variant (PMID 22252923). Therefore, PVS1 can be applied. The highest population minor allele frequency in gnomAD v2.1.1 is 0.00001816 in the European non-Finnish population, meeting PM2. Two individuals meeting the ClinGen LSD VCEP’s specifications for PP4 have been reported who are compound heterozygous for the variant and a unique pathogenic variant; one of these patients is compound heterozygous for the variant and c.525delT, and the other patient is compound heterozygous for the variant and c.2238G>A (p.Trp746Ter) (PMIDs 12897283, 25741864). Therefore, PP4 and PM3 can be applied. Another patient was reported who is compound heterozygous for this variant and a known pathogenic variant (c.525delT), but this data was not included because the GAA activity for the patient was not reported (PMID 14695532). In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. ACMG/AMP criteria met, based on the specifications of the ClinGen LSD VCEP: PVS1, PM2, PM3, PP4.