PM1 is met at moderate strength: the variant alters residues Gln79 and Trp80 within a statistically significant CancerHotspots mutational hotspot in the AKT1 PH domain, a critical functional region with no observed benign variation.¹ PM2 is met at moderate strength: the variant is absent from all gnomAD populations (v2.1 exomes, v4.1 exomes, Canada genomes), with an allele frequency of 0.00%.² Two moderate pathogenic criteria (PM1 + PM2) are insufficient to reach a likely pathogenic classification under generic ACMG/AMP 2015 combination rules (PMID:25741868), which require either 1 very strong + 1 moderate, or 1 strong + 2 moderate, or 2 moderate criteria. The variant is classified as a variant of uncertain significance (VUS).³ PVS1 is not applicable: Mutalyzer normalization resolves the variant to two adjacent missense substitutions (p.Q79K, p.W80G) rather than a null variant.⁴ PS3 (functional studies), PS4 (case-control), PP1 (cosegregation), and multiple other criteria could not be assessed due to absence of variant-specific data in ClinVar, gnomAD, COSMIC, and the literature.⁵