The NM_000152.5:c.1710C>G (p.Asn570Lys) variant in GAA has a minor allele frequency in gnomAD of 0.0001149 in the African population, which is lower than the ClinGen LSD VCEP threshold (<0.001) for PM2_Supporting, meeting this criterion. Functional assays support a deleterious effect of this variant, when expressed in COS cells, this variant was classified as Class B ("potentially less severe") by Kroos et al, 2012 (PMID:22644586). This includes 0.9% GAA activity in cells and 0.5% in medium, and evidence of abnormal synthesis and processing on Western blot. This meets the ClinGen LSD VCEP specifications for PS3_Moderate. Computational evidence is inconclusive, REVEL score = 0.662 which is lower than the LSD VCEP threshold for PP3 (>0.7) and is higher than the LSD VCEP threshold for BP4 (<0.5), and therefore does not meet either criterion. This variant was found in compound heterozygosity (phase unknown) with a pathogenic variant in GAA, c.2560C>T (p.Arg854Ter) in at least one patient with Pompe disease (PMID: 22538254, 22658377, 29122469, 31193175) and another patient with the pathogenic variant c.-32-13T>G and a rare synonymous variant c.1923G>A (p.Leu641=)(PMID: 32248831) (PM3_Supporting). At least two individuals has been reported with this variant and GAA activity <10% normal in lymphocytes/leukocytes/muscle samples/<30% normal in cultured fibroblasts/ in the affected range in a clinically validated dried blood spot assay/ were reported to be on enzyme replacement therapy for Pompe disease (PMID: 17151339, 22538254, 29122469, 32248831)( PP4_Moderate). There is a ClinVar entry for this variant (Variation ID: 555153; 2 star review status) with 2 submitters classifying the variant as a VUS and 1 submitter classifying the variant as likely pathogenic. In summary, this variant meets the criteria to be classified as Likely Pathogenic for Pompe disease. ACMG/AMP criteria met, based on the specifications of the ClinGen LSD VCEP (Specifications Version 2.0): PS3_Moderate, PM3_Supporting, PP4_Moderate, PM2_Supporting (Classification approved by the ClinGen LSD VCEP - Oct. 19, 2021).