This variant, c.1411_1414del (p.Glu471ProfsTer5), is a frameshift variant that is predicted to result in a premature termination codon, nonsense mediated decay, and lack of gene product. Therefore, PVS1 can be applied. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0002513 in the East Asian population, meeting PM2. This variant has been reported multiple times in Asian patients with Pompe disease presenting clinically and identified by newborn screening. At least eight patients with Pompe disease and meeting the ClinGen LSD VCEP’s specifications for PP4 have been reported as compound heterozygous with either c.214C>A (p.Leu141Met), c.872T>C, (p.Leu291Pro), c.1933G>C (p.Asp645His), or c.1935C>A (p.Asp645Glu) (PMIDs 8604985, 18458862, 24243590, 31510962). The in trans data for these patients will be used in the assessment of the missense variants and, therefore, was not included here in order to avoid circular logic. Additional patients with this variant have been reported but were not included because no residual GAA activity provided and, therefore, PP4 could not be assessed (PMIDs 10338092, 25466677, 27183828, 27692865, 28394184, 29122469), or pseudodeficiency alleles are present (PMID 19948615, 21232767, 23632029, 27183828). Of note, the variant has been reported to be in cis with two missense changes, c.[752C>T; 761C>T] (p.[Ser251Leu; Ser254Leu]) (PMIDs 20080426, 25466677, 27183828, 29122469). There is a ClinVar entry for this variant (Variation ID: 188874, 2 star review status) with three submitters classifying the variant as pathogenic, and one as likely pathogenic. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM2, PP4.