This variant, c.1288G>A (p.Glu430Lys) is a missense substitution which has a highest population minor allele frequency in gnomAD of 0.0004332 in the African population. This allele frequency is low enough to meet PM2 based on the allele frequency threshold defined by the ClinGen LSD VCEP (<0.001). Computational analysis, using the meta-predictor REVEL, supports neither a pathogenic nor benign role for this variant; the REVEL score (0.577) is below the ClinGen LSD VCEP’s threshold for PP3 (>0.7) and above the threshold for BP4 (<0.5). To our knowledge, this variant has not been reported in the literature in individuals with Pompe disease, and results of functional studies are not available. However, there is a ClinVar entry for this variant (Variation ID 501777) in which both submitters reported this variant as a variant of unknown significance. One submitter identified the variant in an individual with Pompe disease. However, further clinical and laboratory testing details are unavailable. In summary, this variant meets the criteria to be classified as a Variant of Unknown Significance for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PM2.