1. Mutation, the source of genetic diversity, is the raw material of evolution; however,the mutation process remains understudied, especially in plants. Using both a simulationand reanalysis framework, we set out to explore and demonstrate the improved perfor-mance of variant callers developed for cancer research compared to single nucleotidepolymorphism (SNP) callers in detecting de novo somatic mutations.2. In an in silico experiment, we generated Illumina-like sequence reads spiked withsimulated mutations at different allelic fractions to compare the performance of sevencommonly-used variant callers to recall them. More empirically, we then reanalyzedtwo of the largest datasets available for plants, both developed for identifying within-individual variation in long-lived pedunculate oaks.3. Based on thein silico experiment, variant callers developed for cancer research outper-form SNP callers regarding plant mutation recall and precision, especially at low allele fre-quency. Such variants at low allelic fractions are typically expected for within-individualde novo plant mutations, which initially appear in single cells. Reanalysis of publishedoak data with Strelka2, the best-performing caller based on our simulations, identifiedup to 3.4x more candidate somatic mutations than reported in the original studies.4. Our results advocate the use of cancer research callers to boost de novo mutationresearch in plants, and to reconcile empirical reports with theoretical expectations.Read less <