In human cancers, about 75% of all TP53 alterations are missense mutations, and the eight most frequent (‘hotspot’) missense mutations (R175H, Y220C, G245S, R248Q, R248W, R273H, R273C, and R282W) affect six residues localized in the p53 DNA-binding domain (DBD) and account for 20% of all TP53 mutations (Hainaut and Pfeifer, 2016). The gene discussed is TP53; the disease is cancer.