SMC3 and cancer: While a low MAF at RAD21 p.P298 and its surrounding AA indicates that these positions are rarely mutated in the germline of the non-cancer population (gnomAD database n = 118,479; MAF RAD21 p.P298S < 10−6 and p.P298A < 10−5), high somatic variation frequencies (COSMIC database n = 37,221) are observed at the end of the SMC3 interaction domain and the start of the WAPL/PDS5B interacting domain, where the variants are located (Figure 1E).