Mosaic chromosomal alterations of the autosomes (aut-mCAs) are large structural somatic mutations which cause clonal hematopoiesis and increase cancer risk. Here, we detected aut-mCAs in 1,011,269 participants across four biobanks. Through integrative analysis of the minimum critical region and inherited genetic variation, we found that proto-oncogenes exclusively drive chromosomal gains, tumor suppressors drive losses, and copy-neutral events can be driven by either. We identified three novel inherited risk loci in