Single-nucleotide polymorphisms (SNPs) are recognized as one kind of major genetic variants in population scale. However, polymorphisms at the proteome level in population scale remain elusive. In the present study, we named amino acid variances derived from SNPs within coding regions as single amino acid polymorphisms (SAPs) at the proteome level, and developed a pipeline of non-targeted and targeted proteomics to identify and quantify SAP peptides in human plasma. The absolute concentrations of three selected SAP-peptide pairs among 290 Asian individuals were measured by selected reaction monitoring (SRM) approach, and their associations with both obesity and diabetes were further analyzed. This work revealed that heterozygotes and homozygotes with various SAPs in a population could have different associations with particular traits. In addition, the SRM approach allows us for the first time to separately measure the absolute concentration of each SAP peptide in the heterozygotes, which also shows different associations with particular traits.