At AMP 2025, Heidi Rehm, PhD, outlined new strategies to reduce variants of uncertain significance (VUS), which appear in about one-third of symptomatic genetic tests and complicate clinical decision-making. The forthcoming SVCv4 standards—developed by ACMG, AMP, CAP, and ClinGen—retain the 5-tier system but ease pathways to “likely benign,” inherently lowering VUS rates. SVCv4 also introduces 3 VUS subclasses (Low, Mid, High) to better target follow-up. Additional priorities include robust data sharing, improved computational prediction tools, and scalable functional assays. Together, these initiatives aim to streamline variant interpretation and enhance the clinical utility of genomic testing.