Reported VAR/CNV signals (e.g., TERT, CD274 (PD-L1), JAK2) and HLA associations with PD-1- or CTLA-4-related hypophysitis suggest that a host–tumor–drug triad—rather than a single pathway—drives risk, underscoring the need for HLA/immunogenetic + tumor genomic models to enable pre-therapy stratification [20,22,26]. The gene discussed is CD274; the disease is hypophysitis.