four popular somatic single nucleotide variant snv calling methods varscan somaticsniper strelka and mutect2 were carefully evaluated on the real whole exome sequencing wes depth of 50x and ultra deep targeted sequencing udt seq depth of 370x data the four tools returned poor consensus on candidates only 20 of calls were with multiple hits by the callers for both wes and udt seq mutect2 and strelka obtained the largest proportion of cosmic entries as well as the lowest rate of dbsnp presence and high alternative alleles in control calls demonstrating their superior sensitivity and accuracy combining different callers does increase reliability of candidates but narrows the list down to very limited range of tumor read depth and variant allele frequency calling snv on udt seq data which were of much higher read depth discovered additional true positive variations despite an even more tremendous growth in false positive predictions our findings not only provide valuable benchmark for state of the art snv calling methods but also shed light on the access to more accurate snv identification in the future.