Importantly, when considering highly penetrant pathogenic CNVs, we found a 2:1 male-to-female ratio (deviating from the overall ratio of 6:1 in the study sample). In contrast, the ratio was unchanged among carriers of CNVs characterized by variable expressivity and/or incomplete penetrance. Moreover, among affected subjects, females were twice as likely as males to have exonic deletions involving FMRP targets. Given the sex bias of ASD toward males, it has been suggested that females require a higher genetic load to express ASD,56 and our foundational data support this general hypothesis. This same phenomenon has recently been shown for SHANK157 and the 16p13.11 CNV.58