TP53 and cancer: To robustly assess the performance of different algorithms, we employed five different benchmark datasets: (i) the mutation clustering patterns in protein 3D structures; (ii) literature annotation based on OncoKB [5], a widely used knowledge database in the cancer research community; (iii) the effects of TP53 mutations on their target transcription activity; (iv) the effects of cancer mutations on tumor formation in xenograft experiments; and (iv) functional annotation based on in vitro cell viability assays developed by our group.