A synonymous substitution is the evolutionary substitution of one base for another in an exon of a gene coding for a protein, such that the produced amino acid sequence is not modified.

What mutations are synonymous?

A synonymous mutation is a change in the DNA sequence that codes for amino acids in a protein sequence, but does not change the encoded amino acid. Due to the redundancy of the genetic code (multiple codons code for the same amino acid), these changes usually occur in the third position of a codon.

What is the difference between synonymous and nonsynonymous mutations?

Nonsynonymous mutations change the protein sequences and are frequently subjected to natural selection. The same goes for nonsense mutations that introduce pre-mature stop codons into CDSs (coding sequences). Synonymous mutations, however, are intuitively thought to be functionally silent and evolutionarily neutral.