Pharmacogenomic recommendations are commonly represented as stable mappings from genotype to prescribing action, yet clinical decisions frequently occur in states where genomic prediction is only one determinant of functional drug disposition. Discordance can arise from incomplete variant ascertainment, alternative genotype-to-phenotype translation rules, unequal evidence across genes affecting the same drug, substrate-specific allelic behavior, inhibitory comedications, inflammation, organ dysfunction, and changes in treatment state. These sources of discordance are analytically different and should not be collapsed into a single “conflicting recommendation” category. This Decision Framework Perspective argues that a pharmacogenomic recommendation should be treated as a conditional decision state rather than a permanent property of a genotype. Static genomic evidence should establish a baseline prediction, while current functional modifiers should determine whether that prediction remains applicable at the clinical decision point. The article develops explicit distinctions among baseline genotype-derived phenotype, substrate-specific functional evidence, phenoconversion, comedication effects, disease-mediated metabolic change, and implementation constraints. It further proposes a hierarchical approach in which competing evidence is prioritized by analytical validity, drug specificity, proximity to current functional phenotype, clinical consequence, and uncertainty. The framework is conceptual rather than prospectively validated and is intended to make the assumptions behind genotype-guided recommendations visible, auditable, and revisable.
IJPRAS
