The NM_000152.5(GAA):c.1103G>A variant in GAA is a missense variant predicted to cause substitution of glycine by aspartic acid at amino acid 368 (p.Gly368Asp). This variant has been detected in at least 3 individuals with Pompe disease and deficient enzyme testing. Of those individuals, 3 were compound heterozygous for the variant and the pathogenic variant c.-32-13T>G and 1 of those were confirmed in trans by parental/family testing (PMID: 36246652, 33202836, internal lab data). (PM3 and PP4_Moderate). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). Expression of the variant in HEK293 cells resulted in 2.8% wild type GAA activity – and evidence of abnormal GAA synthesis and processing, indicating that this variant may impact protein function (PMID: 36246652) (PS3_Supporting). The computational predictor REVEL gives a score of 0.647 which is neither above nor below the thresholds predicting a damaging (>0.7) or benign (<0.5) impact on GAA function. There is a ClinVar entry for this variant (Variation ID: 1037598, 1 star review status) with 1 submitter classifying the variant as a VUS. In summary, this variant meets the criteria to be classified as likely pathogenic for Pompe disease based on the ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Storage Disorders Variant Curation Expert Panel (specifications Version 2.0): PM3, PP4_Moderate, PM2_Supporting, PS3_Supporting. (Classification approved by the ClinGen LSD VCEP, December 20, 2022).