Intrinsic variations of the projected density profiles of clusters of galaxies at fixed mass are a source of uncertainty for cluster weak lensing. We present a semi-analytical model to account for this effect, based on a combination of variations in halo concentration, ellipticity and orientation, and the presence of correlated haloes. We calibrate the parameters of our model at the 10 per cent level to match the empirical cosmic variance of cluster profiles at M_200m=10^14...10^15 h^-1 M_sol, z=0.25...0.5 in a cosmological simulation. We show that weak lensing measurements of clusters significantly underestimate mass uncertainties if intrinsic profile variations are ignored, and that our model can be used to provide correct mass likelihoods. Effects on the achievable accuracy of weak lensing cluster mass measurements are particularly strong for the most massive clusters and deep observations (with ~20 per cent uncertainty from cosmic variance alone at M_200m=10^15 h^-1 M_sol and z=0.25), but significant also under typical ground-based conditions. We show that neglecting intrinsic profile variations leads to biases in the mass-observable relation constrained with weak lensing, both for intrinsic scatter and overall scale (the latter at the 15 per cent level). These biases are in excess of the statistical errors of upcoming surveys and can be avoided if the cosmic variance of cluster profiles is accounted for. Show Partial Abstract