Alternative splicing of RNA is the key mechanism by which a single gene codes for multiple functionally diverse proteins. Several studies established compromised RNA homeostasis (splicing errors) and identified previously unknown class of exons, ‘cryptic’ exons, in RNA transcripts. These cryptic exons are often associated with various neurological disorders and cancers. Genome-wise detection of cryptic splice sites can facilitate a comprehensive understanding of the underlying disease mechanisms and develop therapeutic strategies. CrypSplice can effectively quantify and evaluate cryptic splicing patterns from RNASeq data using a beta‐binomial distribution model. CrypSplice, revealed extensive cryptic slicing in Amyotrophic lateral sclerosis and Spinocerebellar ataxia models.