Pyrophosphorolysis activated polymerization (PAP) is a PCR method in which the primer(s) end in an extension terminator which must be removed by pyrophosphorolysis before the primer(s) can be extended. “Pyrophosphorolysis” is simply the reverse of the extension of a primed template by DNA polymerase (i.e., the addition of a dNMP residue to the primer strand). In the “forward” reaction (i.e. the extension of a primed template) pyrophosphate is generated and dNTPs are consumed, as dNMPs are added to the 3′-end of the primer. In the “reverse” reaction (i.e. pyrophosphorolysis) pyrophosphate is consumed and dNTPs are generated as dNMPs are removed from the 3′-end of the primer strand. Primed templates ending in a residue which cannot be extended (a “terminator”) are expected to be subject to pyrophosphorolysis if the polymerase is able to incorporate the terminator and if pyrophosphate is present. In PAP, the use of these blocked primers allows for rare allele detection because pyrophosphorolysis requires a perfectly matched primer:template complex for maximal rate of terminator removal.