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McCaffrey (Achilles/calf) will be placed on injured reserve Saturday, Adam Schefter of ESPN reports.
This move became a clear possibility when McCaffrey didn't practice Friday and was subsequently ruled out for Sunday's Week 2 contest versus Minnesota. McCaffrey will now be required to miss San Francisco's next four contests, thus his earliest return date is Oct. 10 versus Seattle on Thursday Night Football. Jordan Mason will continue to hold lead running back duties for the 49ers for as long as McCaffrey remains sidelined.
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