Coach Kyle Shanahan announced Friday that Garoppolo made it through the week of practice without issue and will step back into his starting job when the Niners host the Miami Dolphins at Levi's Stadium.
"He did a good job," Shanahan said. "Each day it got better, never felt too sore the next day, so we needed to hear that today and see him out there today, and we feel good to go and he'll be starting Sunday."
Garoppolo suffered the ankle injury in the first quarter of a Sept. 20 win against the New York Jets. He played on it through the rest of the first half, but backup Nick Mullens replaced him to open the third quarter and started the past two weeks.
Entering the week, Shanahan expressed optimism that Garoppolo would be ready to play this weekend but wanted to see whether he could handle a week of practice without soreness or a setback. Garoppolo did just that, practicing on a limited basis Wednesday and Thursday and in full Friday. He is not listed on Friday's injury report.
"I got the last couple weeks off to get it right," Garoppolo said Friday. "As far as getting out there, I had the whole week to work on it, so it's feeling pretty good right now."
Garoppolo's return comes at an important time for the Niners, who are coming off a disappointing loss to the Philadelphia Eagles and need a win against the Dolphins before entering a difficult stretch in which they play the Los Angeles Rams, New England Patriots, Seattle Seahawks, Green Bay Packers and New Orleans Saints in consecutive weeks.
C.J. Beathard will serve as Garoppolo's backup this week after replacing Mullens in the closing minutes of last weekend's loss. Shanahan said Wednesday that he didn't want to disclose who would start if Garoppolo couldn't play, but now that Garoppolo will be back, he revealed that Beathard has been promoted to the No. 2 spot instead of Mullens.
Beathard nearly led a last-second comeback against the Eagles, taking the Niners to a touchdown and then having a Hail Mary fall incomplete on the game's final play.
Meanwhile, running back Raheem Mostert's return is a bit more up in the air as he is listed as questionable for Sunday. Mostert has been out since spraining his right knee in Week 2, and the 49ers' run game has struggled in his absence.
Mostert practiced on a limited basis all week but made progress each day. A decision on his status will be made closer to game time Sunday.
"It's really just how he's feeling then," Shanahan said. "He got a little bit more work today. He was able to get through it. We didn't put him through everything but really want to see how that responds tomorrow and how he wakes up tomorrow and how he feels on Sunday."
Receiver Deebo Samuel, who missed practice Thursday and Friday with an illness, is also listed as questionable, though Shanahan said he is feeling OK and it's a matter of getting him through the proper protocols to get back with the team.
This year, players who have an illness other than COVID-19 have to meet certain requirements, including multiple negative COVID-19 tests, to return to the team.
"Deebo is good," Shanahan said. "He says he has no symptoms. He's feeling great, so he's got one more test to pass. I think he did it today. We'll get the results tomorrow on that and then he should be allowed back in the building."
Linebacker Dre Greenlaw (quadriceps) is slated to return this week after missing the past two games, and cornerback Ahkello Witherspoon is questionable with a hamstring injury. Elsewhere on the official injury report, the 49ers ruled out cornerbacks Emmanuel Moseley (concussion) and Dontae Johnson (groin).
Witherspoon's uncertain status and the absence of Moseley and Johnson means the Niners will have to add some help at cornerback before Sunday's game, Shanahan said. The team is expected to place defensive end Ezekiel Ansah (torn biceps) on injured reserve and cornerback K'Waun Williams (sprained knee) on injured reserve on Saturday, which would open two roster spots for additional depth.