Epigenetic modifications play a key role in gene regulation and in recognition of self DNA in bacteria. In-spite of their positive role in cell survival, modifications like cytosine methylation incur a mutational cost. Cytosine methylation, specifically 5-methylcytosine, is prone to hydrolytic deamination which leads to C → T and G → A transitions. Here, we first study the abundance of mutagenic cytosine methylation target motifs and show that bacteria like Vibrio cholerae might use motif avoidance as a strategy to minimize mutational effect of the deamination of methylated cytosine. Second by performing SNP analysis on whole genome sequence data from Vibrio cholerae patient isolates we show a) high abundance of methylation-dependent mutations in the cytosine methylation target motif RCCGGY, b) 95% of these C → T and G → A transitions in the coding region lead to non-synonymous substitutions and c) many of these transitions are associated with membrane proteins and are implicated in virulence. Thus, our SNP analysis of V. cholerae genomes implicates role of cytosine methylation in generating genotypic diversity with adaptive potential.