Significance A series of amyotrophic lateral sclerosis disease-causing mutants of superoxide dismutase have been studied using NMR experiments probing sparsely populated, transiently formed protein conformers. Focusing on the most immature enzyme form, which is monomeric, metal-free, and lacking a stabilizing disulfide bond, we show that the ground states for the wild-type and disease mutant proteins are similar, with an intact eight-stranded β-barrel structure resembling the structure of the mature enzyme. In contrast, conformationally excited states can be affected by mutation, both in terms of the number and types of structures accessible to the mutant. These excited states can play roles in both maturation and aggregation processes and, in the latter case, can provide a variety of possible pathways for aberrant interactions.