Kallikreins (KLKs) are a group of 15 serine proteases encoded by the KLK locus on chromosome 19. Certain single nucleotide variants (SNVs) within the KLK locus have been linked to human disease. Next-generation sequencing of large human cohorts enables reexamination of genomic variation at the KLK locus. We aimed to identify all KLK-related SNVs and examine their impact on gene regulation and function. To this end, we mined KLK SNVs across Ensembl and Exome Variant Server, with exome-sequencing data from 6503 individuals. PolyPhen-2-based prediction of damaging SNVs and population frequencies of these SNVs were examined. Damaging SNVs were plotted on protein sequence and structure. We identified 4866 SNVs, the largest number of KLK-related SNVs reported. Fourteen percent of noncoding SNVs overlapped with transcription factor binding sites. We identified 602 missense coding SNVs, among which 148 were predicted to be damaging. Nine missense SNVs were common (>1% frequency) and displayed significantly different frequencies between European-American and African-American populations. SNVs predicted to be damaging appeared to alter tertiary structure of KLK1 and KLK6. Similarly, these missense SNVs may affect KLK function, resulting in disease phenotypes. Our study represents a mine of information for those studying KLK-related SNVs and their associations with diseases.