Large copy number variants (CNVs) are enriched in the aggregate among severe cases of pediatric disease including neurological and congenital birth defects1,2 as well as neuropsychiatric diseases3–5. Clinical interpretation of individual loci has been problematic for several reasons. First, except for CNV “hotspots” flanked by duplications prone to unequal crossing over and elevated de novo mutation rates6,7, disease associations for many individual CNVs remain unclear due to their rarity and the need to screen extraordinarily large sample sizes. Second, even for CNVs with clear pathogenicity, the dosage-sensitive genes that underlie the phenotypes observed have generally not been identified because the CNVs are large and encompass many genes. Finally, considerable variation in expressivity is often observed, with the same lesion contributing to different disease outcomes8–12. Thus, while their disease risk in general is well established, the phenotypic consequences for most large CNVs are not well characterized nor have these effects been fine mapped. Here, we leverage a collection of data from 15,767 children with various developmental and intellectual disabilities and compare them to a CNV map we generated from 8,329 adult
