Analysis of the protein three-dimensional structure environment. In panel (A) the distribution of the relative solvent accessible area (RSA) for disease-related and neutral variants. The significant difference of their distributions makes the RSA a good feature to discriminate between disease-related and neutral variants. In panel (B) we report the accuracy of SVM-3D predictions as a function of the RSA. The plot shows that the accuracy of SVM-3D is lower in exposed regions with respect to buried ones. Accuracy measures (Q2, C and AUC) are defined in Methods section. DB is the fraction of the whole dataset for disease-related (D) and neutral (N) mutations.