Germany have included 2014 World Cup-winning captain and goalkeeper Manuel Neuer in their final squad for the 2018 tournament, even though he has only just returned from a long-term absence through injury.
Alongside Sane, Bayer Leverkusen duo Bernd Leno and Jonathan also miss out, as does Freiburg striker Nils Petersen.
Fellow Manchester City teammate Kyle walker took to Instagram to show how shocked he was, while fans took to Twitter to reveal their frustration at Sane's ommission from the World Cup.
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The 6ft 1in winger made his debut for Germany in 2016 and has picked up 15 caps, scoring one goal, which came against San Marino in 2017.
He might have shone at club level, but Low's view that Sane has yet to make a real impact on the global stage is not without merit.
This is the most obvious reason to leave Sane out - he plays on the left, where Germany already have Marco Reus and Julian Draxler competing. In the end it was a very tight decision between him and Julian Brandt.
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"Leroy is a huge talent". He had not arrived in global matches yet. Are Brandt and Reus better for Germany's style of play?
"If something happens at the back, we need alternatives, so I had to make that hard decision".
Sane's decision did not go down well with Low, given it was a chance to stake his claim. He was also shortlisted for the PFA Young Player of the Year award.
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"These are four players who had merited their place in the provisional squad through their performances".