within the SwissVar dataset (Fig. 1). From this, we calculated prediction thresholds for our unweighted and weighted methods at which the specificity and sensitivity were both maximized (−3.0 and −1.5, respectively). Using our unweighted method, we noted that the majority of disease-associated AASs (>60%) fell below our threshold, whereas the majority of functionally neutral polymorphisms (80%) fell above this threshold. Furthermore, using our weighted method, the majority of disease-associated AASs (80%) fell below our threshold whereas a significant proportion of functionally neutral polymorphisms (>80%) fell above this threshold.
