The c.868A>G (p.Asn290Asp) variant has a minor allele frequency in gnomAD of 0.00004 in the African population, which is lower than the ClinGen LSD VCEP threshold (<0.001) for PM2_Supporting, meeting this criterion. When expressed in COS cells, this variant was classified as Class E ("presumably nonpathogenic") by Kroos et al, 2012 (PMID:22644586). This includes 71% GAA activity in cells and 38% in medium, and is normally synthesized and processed on Western blot. This meets the ClinGen LSD VCEP specifications for BS3_Supporting. This variant was found in compound heterozygosity (phase unknown) with a unique pathogenic variant in GAA in one patient with Pompe disease (PMID: 32064362) who also meet the ClinGen LSD VCEP's PP4 specifications. Additional cases have been reported (PMID: 22644586) but were not included because the residual GAA activity was not provided (and therefore PP4 cannot be assessed). Based on the ClinGen LSD VCEP's specifications, this data does not meet PM3. REVEL score = 0.561 which is higher than the LSD VCEP threshold for BP4 (<0.5), and therefore does not meet this criterion. There is a ClinVar entry for this variant (Variation ID: 498117; 2 star review status) with 2 submitters classifying the variant as a variant of unknown significance. In summary, this variant meets the criteria to be classified as a Variant of Uncertain Significance 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): PM2_Supporting, PP4_Moderate, BS3_Supporting. (Classification approved by the ClinGen LSD VCEP on Oct 4, 2022).