Our previous combined linkage and association analysis of exome array data in the Cleveland Family Study (CFS) and four cohorts with unrelated individuals (N = 57,234) identified rare, functional variants in RBFOX1, an evolutionarily conserved RNA-binding protein that regulates tissue-specific alternative splicing, to be associated with SBP and PP. In the present study, 487 European Americans (EA) and 507 African Americans (AA) from CFS have been whole-genome sequenced (WGS) as a part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We divided the low frequency and rare variants (defined as minor allele frequency < 5%) of RBFOX1 into three groups: 1) functional coding variants that lead to an amino acid change, 2) synonymous variants, and 3) non-coding variants. The WGS identified 6 variants in group 1, 4 variants in group 2, and 163 variants in group 3 among CFS European Americans; and 12, 4, 269 variants in CFS African Americans, respectively. Using group 1 variants, gene-based analysis using linkage information verified our previous results that rare, coding variants in RBFOX1 are associated with SBP (p-value = 0.00332), DBP (p-value = 0.0267), and PP (p-value = 0.0399) in CFS European Americans. WGS enabled us to identify 3 additional variants in EA that were previously not found in exome array. In African Americans, we detected novel association at the gene-level using functional coding variants (SBP p-value = 0.097; DBP p-value = 0.00663). However, the rare variants associated with BP traits in the two populations are mostly population-specific in this gene, suggesting that rare variant replication at a gene-level is more feasible and necessary than at a variant-level. Replication analysis of RBFOX1 low frequency and rare variants in other TOPMed cohorts are currently underway.