Here, we have assessed the impact of de novo and inherited rare CNV in 2,446 ASD individuals and their parents from the Autism Genome Project (AGP), along with 2,640 unrelated controls, by applying a series of approaches to characterize candidate ASD-associated genes disrupted by CNVs and to identify the biological relationships and common pathways they share. Using evidence from multiple sources, we were able to directly implicate numerous dosage-sensitive genes as risk factors and provide insights into different but related mechanisms underlying ASD.