Starting from the hypothesis that evolutionarily important residues form a spatially limited cluster in a protein's native fold, we discuss the possibility of detecting a non-native structure based on the absence of such clustering. The relevant residues are determined using the Evolutionary Trace method. We propose a quantity to measure clustering of the selected residues on the structure and show that the exact values for its average and variance over several ensembles of interest can be found. This enables us to study the behavior of the associated z-scores. Since our approach rests on an analytic result, it proves to be general, customizable, and computationally fast. We find that clustering is indeed detectable in a large representative protein set. Furthermore, we show that non-native structures tend to achieve lower residue-clustering z-scores than those attained by the native folds. The most important conclusion that we draw from this work is that consistency between structural and evolutionary information, manifested in clustering of key residues, imposes powerful constraints on the conformational space of a protein.