Clonal cytopenia of undetermined significance (CCUS) is associated with an increased risk of developing a myeloid neoplasm with myelodysplasia (MN). To identify the features of the mutant clone(s) that are associated with clinical phenotype and progression, we studied the following cohorts of individuals: 311 patients with idiopathic cytopenia of undetermined significance (ICUS), 532 community-dwelling individuals without hematologic phenotype (n=355) or with unexplained anemia (n=177), and 592 patients with overt MN. Ninety-two of 311 (30%) ICUS patients carried a somatic genetic lesion that allowed diagnosis of CCUS. Clonal hematopoiesis (CH) was detected in 19.7% and 27.7% of non-anemic and anemic community-dwelling individuals, respectively (P=.045). Different mutation patterns and variant allele frequencies (VAF) (clone metrics parameters) were observed in the conditions studied (P<.001). Recurrent mutation patterns exhibited different VAF values associated with marrow dysplasia (0.17-0.48, P<.001), indicating variable clinical expressivity of mutant clones. Unsupervised clustering analysis based on mutation profiles identified two major clusters, characterized by isolated DNMT3A mutations (CH-like cluster) or combinatorial mutation patterns (MN-like cluster), and showing different overall survival (HR=1.8, P<.001). Within CCUS patients, the 2 clusters had different risk of progression into MN (HR=2.7, P<.001). Within the MN-like cluster, distinct subsets with different risk of progression into MN (P<.001) could be identified based on clone metrics. These findings unveil marked variability in the clinical expressivity of myeloid driver genes, and underline the limitations of morphologic dysplasia for clinical staging of mutant hematopoietic clones. Clone metrics appears to be critical to inform clinical decision-making in patients with clonal cytopenia.