This variant, c.525_526del (p.Asn177ProfsTer11), is a frameshift variant that is predicted to result in a premature termination codon, nonsense mediated decay, and lack of gene product, meeting PVS1. This is supported by the finding of this variant in an individual with no GAA cross-reactive immunological material in cultured skin fibroblasts (PMID 22252923, 23825616, 31342611). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003288 in the South Asian population, meeting PM2. One individual with Pompe disease and meeting the ClinGen LSD VCEP’s specifications for PP4 has been reported in the literature (PMID 22252923, 23825616). This patient is homozygous for the variant, meeting PM3_Supporting. Two other individuals with the variant have been reported. One is homozygous (PMID 25455803; different than the individual reported in PMID 25455803 based on the age at diagnosis) another individual who is compound heterozygous for the variant and c.-32-13T>G (PMID 31392188). However, these patients were not included because the residual activity was not provided, and therefore PP4 cannot be assessed, and PM3 was not applied. There is a ClinVar entry for this variant (Variation ID: 189057, 1 star review status) with one submitter classifying the variant 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 specific by the ClinGen LSD VCEP: PVS1, PM2, PM3_Supporting, PP4.