Phenotype-based methods have repeatedly shown to be highly effective in identifying causative variants in whole genome or whole exome sequences. The main limitation of phenotype-based methods, however, is the limited availability of characterised genotype-phenotype associations. Model organism phenotypes have in the past been used to supplement genotype–phenotype associations observed in humans and were demonstrated to predict disease genes. Nevertheless, in almost all cases, genotypes are loss-of-function or gain-of-function variants in single genes. Consequently, phenotypes that arise specifically from abnormal functioning of two or more genes in the same individual are not commonly captured; in the cases in which complex genotypes and their associations with phenotypes are recorded (e.g., in the mouse and fish model organism databases), they are not integrated, not distinguished by the type of interaction between variants, and cannot systematically be queried.