There is a continuous need to identify patients with aggressive disease and therapies they are most likely to benefit from. p53 is known as the “guardian of the genome” and is a commonly mutated gene in cancer. Frequently occurring p53 mutations have been studied in great detail, but have failed to gain clinical utility. With access to mutation data from ~10,000 cancers, it is becoming evident that 75% of p53 mutations are uncommon and it remains to be understood how they affect cancer. In this study we aim to carry out comprehensive analysis of data from ~10,000 tumours to understand how these uncommon p53 mutations contribute to cancer progression. Results from this computational and statistical analyses will be followed by validation in the laboratory. Overall this study will provide insights into the contribution of uncommon p53 mutations to cancer and identify clinical management strategies for these cancers.