Individual proteomes typically differ from the reference human proteome at ∼10,000 single amino acid variants. When viewed on the population scale, this individual variation results in a wide variety of protein sequences. In targeted proteomics experiments, such variability can confound accurate protein quantification. To assist researchers in identifying target peptides with high variability within the human population, we have created the Population Variation plug-in for Skyline, which provides easy access to the polymorphisms stored in dbSNP. Given a set of peptides, the tool reports minor allele frequency for common polymorphisms. We highlight the importance of considering genetic variation by applying the tool to public data sets.