Although most mutations in the SARS-CoV-2 genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. Emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about eleven months. Since late 2020, however, SARS-CoV-2 evolution has been characterised by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence for reduced neutralisation of some SARS-CoV-2 variants by post-vaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update to vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is carried out alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarise the literature on mutations to the SARS-CoV-2 spike protein, the primary antigen, focussing on their impacts on antigenicity and contextualising them in the protein structure, and observed mutation frequencies in global sequence datasets. / The COVID-19 Genomics UK (COG-UK) Consortium is supported by funding from the UK Medical Research Council (MRC), part of UK Research and Innovation, the UK National Institute of Health Research and Genome Research Limited, operating as the Wellcome Sanger Institute.