The NM_000152.5:c.1841C>T variant in GAA is a missense variant predicted to cause substitution of threonine by methionine at amino acid 614 (p.Thr614Met). At least 2 patients with this variant had documented GAA deficiency with <10% of normal mean control level of GAA activity in leukocytes (PP4_Moderate). This variant has been detected in at least 3 individuals with Pompe disease. Of those individuals, 1 was compound heterozygous for the variant and a pathogenic variant (PMID: 33741225). At least 2 individuals were homozygous for the variant (PMID: 33301762, 33741225, 33250842) (PM3). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00004184 (1/23902 alleles) in the African/African-American population, which is lower than the ClinGen LSD VCEP’s threshold for PM2_Supporting (<0.001), meeting this criterion (PM2_Supporting). To our knowledge, the results of functional assays have not been reported for this variant. The computational predictor REVEL gives a score of 0.769 which is above the threshold of 0.7, evidence that correlates with impact to GAA function (PP3). Another missense variant, c.1841C>A (p.Thr614Lys) (ClinVar Variation ID: 167113), in the same codon has been classified as pathogenic for Pompe disease by the ClinGen LSD VCEP (PM5). Splicing prediction using Splice AI revealed no expected effects on splicing due to either of these variants. There is a ClinVar entry for this variant (Variation ID: 286469, 1 star review status) with 3 submitters classifying the variant as uncertain significance, 2 submitters as likely pathogenic, and 1 submitter as pathogenic. 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): PP4_Moderate, PP3, PM3, PM5, PM2_Supporting