Sensitivity of fruit set to the environment is a genetic feature of uncertain origin that limits production in some grapevine clones and cultivars. Here we studied the developmental causes and environmental conditions leading to decreased fruit yield associated to somatic loss of fruit colour in Tempranillo Blanco (TB) white-berried derivative cultivar. We first compared fruit set-related production traits between TB and its black-berried clonal ancestor, Tempranillo Tinto (TT) cultivar, both grown under the same field conditions. We identified that lower cluster weight in TB correlated with a genetic reduction in pollen viability and lower fruit and seed setting. Then, a combination of correlation and two-way-ANOVA (Analysis of Variance) procedures, along with a series of multivariate linear regression models were developed to examine the effect of genotype and pre-flowering environmental factors on the reproductive performance of TB, using data recorded in nine field plots. These analyses identified prolonged pre-flowering cold periods and abundant rainfalls at flowering time as the main conditions increasing the ratio of seedless to seeded berries in the cluster, whereas the low pollen viability and low number of seeds characteristic of TB barely varied across plots. Collectively, these findings indicate that decreased gamete viability caused by complex genome rearrangements is in the origin of increased susceptibility to fruit set disorders in grapevine. The case of TB shows that such dysfunctions can be selected in clonally propagated crops as a trade-off of novel interesting traits emerged after genome reshuffling. This work was funded by the European Community's Seventh Framework Program (FP7/2007–2013) [FP7-311775, Project INNOVINE], the Spanish Ministerio de Economía y Competitividad [BIO2014-59324-R and BIO2017-86375-R] and the Instituto de Estudios Riojanos [2015 ECTR grant to PCB]. JT is funded by a Juan de la Cierva-Incorporación grant [IJC2018-035036-I] .