SANTA CLARA, Calif. -- Nick Mullens will start at quarterback in place of the injured Jimmy Garoppolo for the San Francisco 49ers on Sunday against the New York Giants.
Garoppolo will not be active for the game, leaving C.J. Beathard as Mullens' backup.
All-Pro tight end George Kittle also has been ruled out, the team announced Friday. Kittle, who is working his way back from a sprained left knee, practiced on a limited basis the past two days.
The Niners also will be without running backs Tevin Coleman (knee) and Raheem Mostert (knee), linebacker Dre Greenlaw (quadriceps) and defensive end Dee Ford (back).
From that group, Ford and Kittle are the only ones who also did not play last week. Garoppolo, Mostert, Coleman and Greenlaw suffered injuries against the New York Jets in Week 2. Cornerback Ahkello Witherspoon is also listed as questionable because of a hamstring injury.
Of most importance will be the change at quarterback. Coach Kyle Shanahan indicated Wednesday that it was "most likely" Mullens would start in place of Garoppolo, who has a high right ankle sprain, but he made it official Friday.
Mullens will be making his first start since Dec. 30, 2018, which was the final appearance in an eight-game stretch for him as the starter after Garoppolo tore his left ACL that season. Mullens threw for 2,277 yards with 13 touchdowns and 10 interceptions for a passer rating of 90.8 as the Niners went 3-5 in his starts.
Garoppolo suffered the ankle injury in the first quarter of last week's win against the Jets and played through it before being removed from the game at halftime. Mullens finished the game, going 8-for-11 for 71 yards with an interception as the 49ers rolled to a 31-13 win.
Mullens has taken on the role of starter in practice this week, with Beathard as the backup, as the Niners have trained at The Greenbrier Resort in White Sulphur Springs, West Virginia. Garoppolo did not practice Wednesday, Thursday or Friday.
"He's gotten a lot more reps than he did last time," Shanahan said of Mullens. "But he played pretty well the last time he played and he usually gets most of his reps in camp. He gets a ton in scout team, but it was really good for him this week to get three days in a row with the 1s, and he looked ready to go."
Shanahan also made it clear that Garoppolo will step back into his starting role whenever he's healthy, saying, "When Jimmy is ready to go, he'll be out there."
As for Kittle, there had been some optimism he would return this week after he participated in practice all week on a limited basis. Kittle's sprained left knee was initially thought to come down to a game-time decision, but Shanahan said a conversation with Kittle before Friday's practice removed the need to wait.
"We thought it was a lot safer to leave him out," Shanahan said. "We didn't need to wait another day because of how he sounded today."
The running back situation has also crystallized, as Coleman and Mostert were ruled out. Each has a sprained knee, though Mostert is expected back before Coleman.
That means Jerick McKinnon is likely to make his first start as a Niner since signing with the team in 2018. He missed the past two seasons with a knee injury.
"I'm very confident in Jet," Shanahan said Wednesday. "He's done a great job in all the reps that he's gotten in these two weeks. Every time he's gotten opportunities, he came through for us. Obviously, with those two guys being out, he should get more opportunities this week, and he deserves it. I know he's excited for it, and we're excited to see him."
Jeff Wilson is expected to serve as the backup to McKinnon. Undrafted rookie JaMycal Hasty is likely to get called up from the practice squad for additional depth.
Ford's situation is much murkier. What started as neck spasms became a back injury this week, and Ford has not practiced after not playing against the Jets. Shanahan said for now it's a matter of being patient to see if rest leaves Ford feeling better.
"When you have back issues, sometimes it takes some time, but that stuff will calm down and you'll feel good," Shanahan said. "But if it never does, then you have to do bigger things, and you always want to wait for those bigger things, so you don't know whether it's a day, a week, a month. ... We're doing all that with Dee Ford. I'll be surprised if he's there next week, but I wouldn't rule him out. But that's something that, again, we'll see week to week with that."
With Greenlaw out, the 49ers will likely lean on Azeez Al-Shaair to handle the SAM linebacker job, though Shanahan indicated others could also contribute.
Witherspoon's injury popped up this week, leaving his status in doubt for Sunday, though the Niners are getting cornerback Jason Verrett back from a hamstring injury. If Witherspoon can't play or is limited, Verrett would start in his stead.
In better injury news, Shanahan said receiver Deebo Samuel is closer to returning from a Jones fracture in his left foot. Shanahan said Samuel has looked good in his rehab and has been running routes on the side with no pain this week, though whether he is able to come off injured reserve next week will depend on how he looks.
On the Niners' concerns about the artificial surface at MetLife Stadium, Shanahan said they'd moved past it by Wednesday, when the league took a further look at it and found no issues.
"The NFL has done everything to check it out," Shanahan said. "It's just another turf field. Of course, we'd rather play on grass because it is safer, but that's not something that's on our minds at all anymore. We were a little emotional after the game on it, but I promise that's gone and we are ready to go."