Fig. 4.

Prioritizing variants of uncertain significance (VUSs) from folding free energy differences (∆∆G_Fold) and CADD scores. The ∆∆G_Fold versus CADD score for all classified missense variants (panels a and b) and for all variants including VUSs (panel c) observed in the Deafness Variation Database (DVD). Points are colored according to DVD classification (panels a and c) or model confidence at the variant’s amino acid position (panel b). CADD score and ∆∆G_Fold show a positive correlation. A high ∆∆G_Fold and high CADD score in confident regions of a protein model favor pathogenic variants; low ∆∆G_Fold and low CADD score favor benign variants and exhibit greater variety in model confidence. Prioritized VUSs have both high ∆∆G_Fold and high CADD scores