Background: Taxane-induced peripheral neuropathy (TIPN) is one of the most important survivorship issues for cancer patients. African Americans (AA) have previously been shown to have an increased risk for this toxicity. Germline predictive biomarkers hold promise to help identify a priori which patients might be at extraordinarily high risk for this toxicity. Methods: We performed whole exome sequencing on germline DNA from AA patients who received a standard dose and schedule of paclitaxel in the adjuvant, randomized phase III breast cancer trial, E5103. Evaluable cases were defined as those with either grade 3-4 (n = 56) or grade 2-4 (n = 121) TIPN and were compared to evaluable controls (n = 59) who had no evidence of TIPN. We retained for analysis rare variants with a minor allele frequency < 3% and which were predicted to be deleterious by protein prediction programs. A gene-based, case-control analysis using SKAT was performed to identify genes that harbored an imbalance of deleterious variants associated with increased risk of TIPN. Results: Five genes had a p-value < 10^-4 for grade 3-4 TIPN analysis and three genes had a p-value < 10^-4 for the grade 2-4 TIPN analysis. For the grade 3-4 TIPN analysis, SET binding factor 2 (SBF2) was significantly associated with TIPN (p-value = 4.35 x10^-6). Five variants were predicted to be deleterious in SBF2. Inherited mutations in SBF2 have previously been associated with autosomal recessive, Type 4B2 Charcot-Marie-Tooth (CMT) disease. Conclusions: Rare variants in SBF2, a CMT gene, predict an increased risk of TIPN in AA patients receiving paclitaxel.