Verifying the association of common putative ASXL1 variants with age can help distinguish true variants from recurrent artifacts. (A) Association of all ASXL1 variants present ≥20 times in the UKB exome data set and ≥15 times in the All of Us whole genome data set. Variants not associated with age- or a CHIP-associated TERT promoter variant (rs7705526) are colored in red. Variants associated with rs7705526 only are colored in blue. (B-C) Association of ASXL1 G646Wfs∗12 and G645Vfs∗58 with age across VAF strata identifies specific large VAF subsets of G646Wfs∗12 as somatic mutations, whereas G645Vfs∗58 appears to be an artifact of exome sequencing that is not present in All of Us. (D) There is a significant association of ASXL1 variants passing filtering with myeloid cancer, death, and smoking, but a minimal association with variants that were removed, supporting that these removed variants are artifacts.