For classic Ehlers-Danlos syndrome, up to 40% of the disease is caused by variation in the COL5A1 gene.20 Taking 0.4 as our maximum allelic contribution, and a population prevalence of 1/20,000,20 we derive a maximum tolerated ExAC AC of 5 (Table 2). This evidence concerns the gene COL5A1 and Ehlers-Danlos syndrome.