A computer implemented method for validating variant calls, the method comprising: under control of one or more processors executing program instructions for, receiving sequencing data including a sample read that has a corresponding sequence of nucleotides along a genomic sequence of interest; receiving an indication of a potential variant call at a designated position within the sequence of nucleotides along the genomic sequence of interest; obtaining baseline variant frequencies at the designated position within one or more baseline genomic sequences, wherein a baseline frequency represents the relative frequency of a variant at a particular position along one or more baseline genomic sequences in a population, wherein the population corresponds to the number of reads and/or samples obtained from the one or more baseline genomic sequences from a population of normal individuals; obtaining a sample variant frequency at the designated position for the genomic sequence of interest, wherein a sample variant frequency represents the relative frequency of a variant at a particular position along the genomic sequence of interest in a population, wherein the population corresponds to the number of reads and/or samples obtained for the genomic sequence of interest from an individual; obtaining a quality score by analyzing the baseline and sample variant frequencies at the designated position; and validating the potential variant call for the genomic sequence of interest based on the quality score, wherein the validating comprises comparing the quality score to a threshold, wherein obtaining the baseline variant frequencies comprises: a. receiving sequencing data from a plurality of reference reads of a sequence of nucleotides along the baseline genomic sequence, for a set of positions within a current base pair window, wherein a length of the current base pair window comprises a plurality of base pairs; b. identifying a candidate variant frequency for one or more positions in the set of positions within the current base pair window; c. selecting one of the candidate variant frequencies as the baseline variant frequency for a designated position within the reference read; and d. shifting the base pair window along the baseline genomic sequence and repeating the operations at a, b, and c. under control of one or more processors executing program instructions for, receiving sequencing data including a sample read that has a corresponding sequence of nucleotides along a genomic sequence of interest; receiving an indication of a potential variant call at a designated position within the sequence of nucleotides along the genomic sequence of interest; obtaining baseline variant frequencies at the designated position within one or more baseline genomic sequences, wherein a baseline frequency represents the relative frequency of a variant at a particular position along one or more baseline genomic sequences in a population, wherein the population corresponds to the number of reads and/or samples obtained from the one or more baseline genomic sequences from a population of normal individuals; obtaining a sample variant frequency at the designated position for the genomic sequence of interest, wherein a sample variant frequency represents the relative frequency of a variant at a particular position along the genomic sequence of interest in a population, wherein the population corresponds to the number of reads and/or samples obtained for the genomic sequence of interest from an individual; obtaining a quality score by analyzing the baseline and sample variant frequencies at the designated position; and validating the potential variant call for the genomic sequence of interest based on the quality score, wherein the validating comprises comparing the quality score to a threshold, wherein obtaining the baseline variant frequencies comprises: a. receiving sequencing data from a plurality of reference reads of a sequence of nucleotides along the baseline genomic sequence, for a set of positions within a current base pair window, wherein a length of the current base pair window comprises a plurality of base pairs; b. identifying a candidate variant frequency for one or more positions in the set of positions within the current base pair window; c. selecting one of the candidate variant frequencies as the baseline variant frequency for a designated position within the reference read; and d. shifting the base pair window along the baseline genomic sequence and repeating the operations at a, b, and c. a. receiving sequencing data from a plurality of reference reads of a sequence of nucleotides along the baseline genomic sequence, for a set of positions within a current base pair window, wherein a length of the current base pair window comprises a plurality of base pairs; b. identifying a candidate variant frequency for one or more positions in the set of positions within the current base pair window; c. selecting one of the candidate variant frequencies as the baseline variant frequency for a designated position within the reference read; and d. shifting the base pair window along the baseline genomic sequence and repeating the operations at a, b, and c.