PAM (Point Accepted Mutation) uses sequence data for proteins which can be aligned with 99% identical sequence. In such aligned sequences, one counts the frequency of each residue, and of each pair of residues in a "column".
Recall: using p(a,b) = prob. that a (amino acid residue) mutated into b.
Basically, the score s(a,b) from this data is a "LOD score":
s(a,b) = log(p(a,b)/p(a)p(b)).
Comparison of two "models": significant association vs. independent randomness.