Advances in DNA sequencing technology mean chromosomal deletions are increasingly found in healthy individuals and also in patients with a wide range of developmental abnormalities. Understanding the contribution of each deletion to the clinical picture is challenging. In this work, as an example of this common phenomenon, we analysed 41 patients with simple deletions of chromosome 16, which cause a disease called ATR-16 syndrome. We find the risk of developmental and neurological abnormalities arises from much smaller deletions than previously reported and disease severity increases with deletion size, however, we find no “critical chromosomal regions” that determine the impact of deletions. Instead, we find evidence coinherited mutations elsewhere in the genome explain the variable effects of chromosomal deletions on human health. (By Dr. Christian Babbs, https://jmg.bmj.com/content/early/2020/01/31/jmedgenet-2019-106528 )