Although several drug and protein databases contain variant data, the effect of drugs on specific variants is very sparse and conflicting The variant landscape in ChEMBL 31 and additional Papyrus sources is, as expected, a reflection of the clinical relevance and interest of the community in particular organisms, protein families, targets, and individual variants. Unsurprisingly, human proteins concentrated the bulk of the variant data, but several mammalian orthologs and human pathogens were also identified. Of note, curated drug resistance databases for significant pathogens such as HIV , tuberculosis , and other antibiotic-resistant bacteria are available independently of bioactivity databases and should be queried separately. Apart from being more complete, these databases have a more domain-focused curation process e.g. strain annotation in microorganisms. Although different organisms show significant differences in the amounts of data available, the amino acid substitution trends align with nature-observed patterns. Indeed, organisms with smaller genome sizes and higher mutation rates, such as viruses and to a lesser extent bacteria, accumulated larger amounts of non-disrupting substitutions compared to human proteins .