 This study suggests that the presence of deleterious mutations in the human genome may not necessarily lead to disease, but instead may depend on the context of the mutations' location within the interactome. Specifically, mutations located in peripheral regions of the interactome appear to have little effect on the overall integrity of the interactome, while mutations located in central regions can have a greater impact. Additionally, mutations causing monogenic diseases appear to be located in a middle ground between the two extremes.