a, Estimation of the reduction in power due to size differences between non-coding elements and genes (median 600 bp versus 1,800 bp) and ignoring VEP annotations used to stratify benign from likely damaging variants. Dots and bars represent the point estimate and 95% confidence interval, respectively. b, Credible intervals for the proportion of fetal brain-active conserved elements and proportion of sites within those elements with a dominant mechanism for developmental disorders. c, Power calculations for disease-associated non-coding element discovery. Without annotation or tools to discriminate pathogenic from benign variants in non-coding elements (grey), more than 100,000 trios are required to achieve 40% power. With annotation or tools to fully discriminate likely pathogenic from benign variants (blue), 40% power is achieved with only 21,000 trios.