Nche was forced off the pitch after an awkward collision with Japan skipper Warner Dearns in the opening 20 minutes of the game and was subsequently replaced by Gerhard Steenekamp.
It was Steenekamp's first game for the Springboks this year, with the loosehead prop struggling with an injury of his own, but he continued the strong work of Nche, particularly in the scrums, playing over an hour.
His return from injury and full fitness has proven to be rather timely as it eases a potential loosehead prop crisis with coach Rassie Erasmus confirming that Nche's tour is over.
"It's serious, I don't think he will play for the rest of the tour," Erasmus said.
"Unfortunately, in the tackle situation, he hurt his ankle and his knees - he is on crutches, I don't think we will have him for the rest of the tour."
In Steenekamp's absence earlier this year, Edinburgh prop Boan Venter made his Test debut against Georgia and has since gone on to make four further caps.
Venter didn't play against Japan, possibly because he was available due to the match being outside of the official World Rugby international window, which is also true for Bath's Thomas du Toit.
While Du Toit has mostly played tighthead for club and country recently, he is capable of switching sides of the scrum with ease, and Erasmus says that he will be asked to do so again with tighthead prop Asenathi Ntlabakanye likely to be called in as injury cover for Nche.
"We are planning to replace him. We've got Boan Venter and Gerhard Steenekamp, who played really well, then Thomas du Toit is back, and then we have Wilco Louw and Zach Porthern," the Bok boss added.
"But if another loosehead goes down in the week, we are in a bit of trouble, so we will probably get Asenathi Ntlabakanye in, but I do need to talk to the selectors first. But thinking about it right now, Asenathi will come in and then Thomas will swing between tighthead and loosehead for us.
"I just need to get the go-ahead from the selectors, but that's where our heads are currently."
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Ntlabakanye also made his Test debut earlier this year, but was released from the Springboks squad after returning an "adverse analytical finding" during random testing.
Despite failing the test, he has not been provisionally banned and is free to play while he contests the finding. The prop was also in action this week in England, featuring for the Barbarians in their clash against the All Blacks XV. He scored a try for the Baa-Baas, who fell to a 19-33 defeat to the New Zealanders.
Nche's injury is a further blow to the front row stocks after Jan-Hendrik Wessels, who plays loosehead and hooker, failed in his appeal for a nine-week ban, which has been reduced by a week.