The proper identification of splice sites has to be highly precise as the consensus splice sequences are very short and there are many other sequences similar to the authentic splice sites within gene sequences, which are known as cryptic, non-canonical, or pseudo splice sites. When an authentic or real splice site is mutated, any cryptic splice sites present close to the original real splice site could be erroneously used as authentic site, resulting in an aberrant mRNA. The erroneous mRNA may include a partial sequence from the neighboring intron or lose a partial exon, which may result in a premature stop codon. The result may be a truncated protein that would have lost its function completely.
Shapiro–Senapathy algorithm can identify the cryptic splice sites, in addition to the authentic splice sites. Cryptic sites can often be stronger than the authentic sites, with a higher S&S score. However, due to the lack of an accompanying complementary donor or acceptor site, this cryptic site will not be active or used in a splicing reaction. When a neighboring real site is mutated to become weaker than the cryptic site, then the cryptic site may be used instead of the real site, resulting in a cryptic exon and an aberrant transcript.
Numerous diseases have been caused by cryptic splice site mutations or usage of cryptic splice sites due to the mutations in authentic splice sites.