The variant had a combined annotation-dependent depletion (CADD) score of 29.7, exceeding the gene-specific mutation significance cutoff (16.4, 99% confidence interval), and being comparable to pathogenic DNABD variants M394T, N401D, E415L, and E415K, as well as a pathogenic Src homology 2 domain variant previously reported in STAT3 GOF patients and various neoplasms (Y640F) [17, 28, 29] (Fig. 1D and E). Here, STAT3 is linked to neoplasm.