Mutations resulting in the disruption of protein function are the underlying causes of many genetic diseases. Some mutations affect the number of expressed proteins while others alter the activity on a per-molecule basis. Single amino acid substitutions as caused by non-synonymous Single Nucleotide Polymorphisms (nsSNPs) often disrupt function by altering protein structure and/or stability, but can also wreak havoc by directly impacting functional binding sites. Given the experimental three-dimensional (3D) structure of a protein, we can try to differentiate between the effect on structure/stability and the effect on binding. However, experimental 3D structures are available for only 1% of all known proteins, the magnitude of stability change caused by a given mutation is more widely available.