As before, we interrogate the amino acid probabilities within the most informative SUPERFAMILY [Gough et al., 2001] or Pfam [Sonnhammer et al., 1997] (Pfam-A and Pfam-B) HMM (as measured by the Kullback–Leibler [Kullback and Leibler, 1951] divergence from the SwissProt/TrEMBL [Apweiler et al., 2004] amino acid composition). However, for an improved performance in human, the predicted magnitude of effect is weighted by the relative frequency of disease-associated (HGMD) and functionally neutral (UniProt) AASs mapping onto the relevant SUPERFAMILY/Pfam HMM:
