In genetics, a neutral mutation is a mutation that occurs in an amino acid codon (presumably within an mRNA molecule) which results in the use of a different (but often chemically similar) amino acid that has a negligible effect on fitness. This is similar to a silent mutation, where a codon mutation may encode the same amino acid (see Wobble Hypothesis); for example, a change from AUU to AUC will still encode leucine, so no discernible change occurs (a silent mutation).

A neutral mutation may or may not affect the resulting protein. For example, if the codon AAA is mutated to AGA, arginine would be used in the resulting protein instead of lysine. These amino acids are chemically very similar and may not have any appreciable effect on the protein or its function; alternately, a mutation may in fact be lethal, or prevent the protein from functioning correctly or at all (in this case, it would become a missense mutation).

If the mutation changes the original amino acid codon to a stop codon, it would be termed a nonsense mutation. Among humans, roughly 95% of all mutations can be classified as neutral mutations, with roughly 5% being missense mutations.