The NM_000152.5:c.1409A>C variant in GAA is a missense variant predicted to cause substitution of Asn by Thr at amino acid 470 (p.Asn470Thr). The highest population minor allele frequency in gnomAD v4.0.0 is 0.0001068 (8/74918 alleles) in the African population, which is lower than the ClinGen Lysosomal Diseases VCEP’s threshold for PM2_Supporting (<0.001), meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.468 which is below the threshold of 0.5, evidence that does not predict a damaging effect on GAA function (BP4). It has been reported in two cases identified as affected by newborn screening (PMID 23430949, 37087815). There is insufficient data to apply PP4. There is a ClinVar entry for this variant (Variation ID: 526525, 2 star review status) with 3 submitters classifying the variant as Uncertain significance. In summary, this variant meets the criteria to be classified as Uncertain significance for Pompe disease based on the ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert panel (specifications Version 2.0): PM2_supporting. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on December 19, 2023).