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Background: Climate change is arguably a major threat to biodiversity conservation and there are several methods to assess its impacts on species potential distribution. Yet the extent to which different approaches on species distribution modeling affect species richness patterns at biogeographical scale is however unaddressed in literature. In this paper, we verified if the expected responses to climate change in biogeographical scale—patterns of species richness and species vulnerability to climate change—are affected by the inputs used to model and project species distribution. Methods: We modeled the distribution of 288 vertebrate species (amphibians, birds and mammals), all endemic to the Amazon basin, using different combinations of the following inputs known to affect the outcome of species distribution models (SDMs): 1) biological data type, 2) modeling methods, 3) greenhouse gas emission scenarios and 4) climate forecasts. We calculated uncertainty with a hierarchical ANOVA in which those different inputs were considered factors. Results: The greatest source of variation was the modeling method. Model performance interacted with data type and modeling method. Absolute values of variation on suitable climate area were not equal among predictions, but some biological patterns were still consistent. All models predicted losses on the area that is climatically suitable for species, especially for amphibians and primates. All models also indicated a current East-western gradient on endemic species richness, from the Andes foot downstream the Amazon river. Again, all models predicted future movements of species upwards the Andes mountains and overall species richness losses. Conclusions: From a methodological perspective, our work highlights that SDMs are a useful tool for assessing impacts of climate change on biodiversity. Uncertainty exists but biological patterns are still evident at large spatial scales. As modeling methods are the greatest source of variation, choosing the appropriate statistics according to the study objective is also essential for estimating the impacts of climate change on species distribution. Yet from a conservation perspective, we show that Amazon endemic fauna is potentially vulnerable to climate change, due to expected reductions on suitable climate area. Climate-driven faunal movements are predicted towards the Andes mountains, which might work as climate refugia for migrating species. [ABSTRACT FROM AUTHOR]