ACMG/AMP Variant Classification ACMG Reasoning Each criterion (PS, PM, PP for pathogenic; BS, BP for benign) contributes a weighted piece of evidence for or against pathogenicity. The classification is the COMBINATION of all activated criteria, not any single criterion. Do not overweight a single finding. The hierarchy is: PVS1 (very strong) PS (strong) PM (moderate) PP (supporting). On the benign side: BA1 (stand-alone) BS (strong) BP (supporting). A frameshift in a LOF-intolerant gene (PVS1) plus a ClinVar expert-panel pathogenic entry (PS1) is pathogenic. A single PP criterion alone is not…