The NM_000152.5:c.2702T>A variant in GAA is a missense variant predicted to cause substitution of leucine by glutamine at amino acid 901 (p.Leu901Gln). At least one patient with this variant had documented GAA deficiency with 5.4% of normal mean control level of GAA activity in muscle and undetectable GAA activity in cultured fibroblasts (PP4_moderate). This patient presented at 8 months of age with moderate proximal muscle weakness and elevated CK with mild left ventricular hypertrophy without cardiac insufficiency. The patient was classified as having childhood onset Pompe disease (PMID: 15145338). This individual was compound heterozygous for the variant and a second pathogenic GAA variant confirmed in trans by parental testing (PM3). This variant is absent in gnomAD v4.1.0. (PM2_Supporting). When expressed in COS cells, this variant resulted in <1% GAA activity using 4-MUG and glycogen substrates. Western blot of transfected cell lysates showed impaired processing of the precursor protein to the mature form (PS3_moderate). The computational predictor REVEL gives a score of 0.923 which is above the threshold of 0.7, evidence that correlates with impact to GAA function (PP3). There is a ClinVar entry for this variant (Variation ID: 2585303). In summary, this variant meets the criteria to be classified as Likely Pathogenic for Pompe disease based on the GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 2.0): PP4_moderate, PM3, PM2_supporting, PS3_moderate, PP3 (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel, August 4, 2026)