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We propose the conditional predictive impact (CPI), a consistent and unbiased estimator of the association between one or several features and a given outcome, conditional on a reduced feature set. Building on the knockoff framework of Candès et al. (J R Stat Soc Ser B 80:551–577, 2018), we develop a novel testing procedure that works in conjunction with any valid knockoff sampler, supervised learning algorithm, and loss function. The CPI can be efficiently computed for high-dimensional data without any sparsity constraints. We demonstrate convergence criteria for the CPI and develop statistical inference procedures for evaluating its magnitude, significance, and precision. These tests aid in feature and model selection, extending traditional frequentist and Bayesian techniques to general supervised learning tasks. The CPI may also be applied in causal discovery to identify underlying multivariate graph …