Functional activity of population-level missense variants in IFIH1. (A) IFNB1-driven luciferase activity of overexpressed IFIH1 variants, measured as means % of the wild-type from at least three independent experiments, plotted against CADD score (A) or MAF (B). Black, missense variants. Orange, patient K365E variant. Red, loss-of-function (nonsense, splice acceptor/donor, frameshift) variants. Blue, gain-of-function variants. MSC, mutation significance cutoff. Variant information with corresponding plotted values (100 ng of construct) are presented in Table S3.