This has important implications for the allelic architecture of disease. Based on sheer numbers, nucleotide substitutions probably account for the majority of disease risk alleles, but based on sheer size and potential to impact genes (or multiple genes), structural mutations are more pathogenic on average. Thus, we expect that CNVs as a class, and de novo CNVs in particular, will be more enriched in variants that have large effect on disease risk. Perhaps naturally, the early insights into the rare genetic causes of common disease have emerged from these classes of variants.
