This variant, c.545C>G (p.Thr182Arg), has not been reported in any patients with Pompe disease, to our knowledge, and the results of functional studies are not available. A patient who is heterozygous for the variant and who has limb girdle muscle weakness has been reported. A second variant was not identified and the authors concluded that GAA deficiency was highly unlikely to be the cause of this patient's symptoms (PMID 29149851). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001 in the European non-Finnish population, meeting PM2. The score for the in silico meta-predictor, REVEL, suggests that the amino acid change is not deleterious. The in silico splicing tools MaxEntScan and Human Splicing Finder suggest that this variant, which alters the second to last nucleotide of exon 2 in GAA, may affect normal splicing. However, the predicted impact is not consistent between the two slicing predictors. Therefore, neither PP3 nor BP4 is met. There is a ClinVar entry for this variant (Variation ID: 499380, 2 star review status) with two submitters both classifying the variant as uncertain significance. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PM2.