CRISPR base-editing technology allows for the introduction of point mutations into DNA without the introduction of toxic double strand breaks. Advances have made this technology scalable and efficient, with the two main DNA base-editors enabling conversion of C•G to T•A base pairs or A•T to G•C base pairs. By mapping the outcomes of large-scale base-editing mutagenesis screens, performed at The Wellcome Sanger Institute, back to protein structural information, this joint project will investigate the impact of genetic variation on protein structure and function, facilitating the identification of novel druggable domains.