The NM_000152.5:c.796C>A variant in GAA is a missense variant predicted to cause substitution of proline by threonine at amino acid 266 (p.Pro266Thr). One patient with a diagnosis of Pompe disease has been reported who is compound heterozygous, phase unknown, for the variant and a variant in GAA that has been classified as pathogenic by the ClinGen LD VCEP, c.2237G>A (p.Trp746Ter) (PMID: 29451150) (PM3_Supporting). Two other missense changes, c.796C>T (p.Pro266Ser) and c.797C>T (p.Pro266Leu) at the same amino acid residue have been reported. The first, c.796C>T (p.Pro266Ser), has been classified as likely pathogenic by the ClinGen LD VCEP. The second variant, c.797C>T (p.Pro266Leu), has not yet been classified as pathogenic or likely pathogenic by the ClinGen LD VCEP (PM5_Supporting). Expression of the variant in HEK293 cells demonstrates loss of GAA activity, and western blot shows only the 110kDa precursor band suggesting abnormal GAA processing (using the assay reported in PMID: 36246652). The computational predictor REVEL gives a score of 0.262 which is below the threshold of 0.5, evidence that does not predict a damaging effect on GAA function (BP4). There is a ClinVar entry for this variant (Variation ID: 1693549). In summary, this variant meet the criteria to be classified as a variant of uncertain significance for Pompe disease. GAA-specific ACMG/AMP codes met, based on the specifications of the ClinGen LD VCEP (Specifications Version 2.0.0): PS3_Moderate, PM2_Supporting, PM3_Supporting, PM5_Supporting, BP4.