Over 300 mutations in the OTC gene have been identified in patients, with the majority being single base alterations that alter the amino acid code.
Most families have "private" mutations, with recurrent mutations typically found at CpG dinucleotides. CpG dinucleotides tend to be mutation hotspots.

The maximum number of single base polymorphisms using the OTC mRNA sequence to be close to 3195, obtained by summing the possible changes for each codon by only changing one base at a time (3*3*355 codons). Of these, 152 result in a mutation that causes a stop codon (TGA, TAA,TAG), 740 of these changes do not affect the amino acid code (synonymous mutations; ie: CCT, CCC, CCA, CCG all code for proline), and 2303 result in changes that affect the amino acid sequence (nonsynonymous mutations). This analysis does not correctly account for mutations at the splice junctions, or for mutations that may affect cryptic splice sites but provides an approximate estimate of the diversity of mutations.