Abstract: Methods of calling genomic sequence values in complex calling regions are disclosed. Following a preliminary sequence alignment a complex calling region may be identified where no sequence values satisfy preliminary alignment criteria. Potential hypotheses may be formulated for the complex calling region and the probability of each hypothesis representing a correct alignment may be calculated by evaluating the probability of each hypothesis being correct for the reads and the probability of each hypothesis occurring. The hypothesis best satisfying hypothesis selection criteria may be selected. The method may include an evaluation of possible indels in the complex calling region.