We have now used CRISPR/Cas9 to create knock-in mice expressing synonymous variable-CpG (vc) Trp53 exons 5–8, and thus to test whether germline expression of one or both of these CpG extremes causes embryogenetic defects, impaired fertility, shortened survival, or altered susceptibility to spontaneous cancers, despite the predicted absence of change in the amino acid sequence of p53 proteins encoded. The gene discussed is TP53; the disease is cancer.