The NM_000152.5:c.1552-3C>G variant in GAA is an intronic variant which occurs within intron 10 and is predicted to impact splicing by disrupting the acceptor splice site (PP3). Experimental studies in fibroblasts from a patient that was homozygous for the variant demonstrated that the variant results in the full inclusion of intron 10, which is predicted to introduce a premature termination codon. However, there was some evidence of normal splicing (PMID 6838077, 25243733) (PS3_Moderate). At least 3 patients with Pompe disease have been reported with this variant including 2 patients with documented GAA deficiency (PP4_Moderate) (PMID 16838077, 28196920, 23430949). Of these patients, one is homozygous for the variant (PMID 16838077) and one is compound heterozygous for the variant and c.-32-13T>G, phase unknown (PMID 16838077) (PM3). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0002713 (35/129024 alleles) in the European (non-Finnish) population, which is lower than the ClinGen LSD VCEP’s threshold for PM2_Supporting (<0.001), meeting this criterion (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 419722, 2 star review status) with 10 submitters classifying as likely pathogenic or pathogenic and 1 submitter classifying as a variant of uncertain significance. In summary, this variant meets the criteria to be classified as likely pathogenic for Pompe disease. GAA-specific ACMG/Amp criteria met, as specified by the ClinGen LSD VCEP: PM3, PS3_Moderate, PP4_Moderate, PP3, PM2_Supporting. Classification approved by the ClinGen LSD VCEP on May 16, 2022.