Our analyses of somatic mutations in antiviral Ab led to an unexpected finding: CDR AGY Ser codons frequently mutated to Asn, Thr, and Gly codons in addition to Arg codons. Most of these mutations occurred by single-base changes, predominantly at the central base in the AGY triplet (Table 2), which is the position that is preferentially targeted by AID (13). In many cases, mutations to these alternative codons, particularly those for Asn and Thr, were more frequent than to Arg codons. For example, in anti-influenza Abs, CDR AGY mutations to Asn and Thr codons were each approximately twice as frequent as mutations to Arg codons. These observations were particularly revealing because in their analyses of numerous crystal structures of Ab–Ag complexes, Raghunathan et al. (19) identified Asn, Thr, Arg, Gly, Ser, Asp, and Tyr as key (i.e., most frequent) Ag-contact residues.