San Francisco 49ers lose LT Trent Williams to high ankle sprain on game-turning play at Denver Br...

DENVER -- On the play that swung Sunday night's contest in theDenver Broncos' favor, the San Francisco 49ers gave up two points via safety and possession of the ball in a game they'd go on to drop by a point. But the biggest loss on that play was the injury that Pro Bowl left tackle Trent Williams suffered at the end of it.

Williams departed the11-10 loss to the Broncos with what the Niners believe is a high right ankle sprain, coach Kyle Shanahan said after the game. While no timetable for a return is set, the injury is expected to cost Williams some time.

Losing Williams, regardless of duration, will be difficult for the Niners to overcome, especially on an offensive line featuring three new starters on the interior and right tackle Mike McGlinchey still working back to form after a season-ending quadriceps injury in 2021.

"It's tough," San Francisco quarterback Jimmy Garoppolo said. "Trent's a warrior. Hopefully, he bounces back fast, but it's always tough when you lose a guy like that, especially the leadership that he brings to this team. The poise and everything that he brings, it will be tough to replace that. But we've got to."

Williams' injury came on a disastrous play for the Niners in which Garoppolo took the snap at San Francisco's 1 and lost track of where he was in the end zone. He stepped on the end line for a safety, trimming the 49ers' lead to 7-5.

On the play, which took place with 9:53 to go in the third quarter, Williams blocked his defender on the left edge as Niners center Jake Brendel engaged Broncos defensive tackle D.J. Jones.

As Brendel appeared to finish his block, he shoved Jones, who rolled into Williams' right leg. Williams went down and immediately grabbed at the ankle. A cart was quickly brought out for Williams, but he declined it and hobbled to the X-ray room at the south tunnel with some help from 49ers medical personnel.

The Niners initially turned to Jaylon Moore, a 2021 fifth-round pick out of Western Michigan, to replace Williams at left tackle. But Colton McKivitz, a fifth-round pick in 2020 out of West Virginia, stepped in for Moore on the game's final drives.

McKivitz has traditionally been Williams' primary backup, but McKivitz was dealing with an ankle injury in practice during the week, which meant Moore got the first call in Denver.

Neither Moore nor McKivitz fared particularly well. Moore gave up a sack to Broncos linebacker Randy Gregory on his first pass protection attempt.

The Niners' offense sputtered Sunday night, turning the ball over three times, surrendering the safety and finishing 1-of-10 on third down.

"[Trent is] as important to our football team as anybody is," McGlinchey said. "Colton stepped up, and he's had an unbelievable last year and some change, and he's ready for that. Jaylon Moore is capable of playing in that role. We have guys to fill the spot, which is a good thing; but obviously, it's impossible to replace a Trent Williams, and that hurts our football team, for sure."

For Williams, this is the second high right ankle sprain he has dealt with in less than nine months. He suffered a similar injury in a playoff win against the Green Bay Packers on Jan. 22, but he played through it in the NFC Championship Game against the Los Angeles Rams.

Williams said in June he wished he hadn't attempted to play through the injury in January, acknowledging he "probably shouldn't have pushed it that far" and noting that McKivitz would have played better on two healthy ankles.

Whoever steps in for Williams now will have big shoes to fill.

"He's the best football player in the NFL," 49ers tight end George Kittle said. "It's nothing against the guys below him, but there's no one that is nearly as good as Trent Williams, so when you lose him and also a captain, the most steady player on our team besides probablyNick [Bosa], it's just tough."

In addition to Williams, Niners linebacker Azeez Al-Shaair also left Sunday's contest and did not return. Shanahan said the belief is that Al-Shaair has a sprained MCL, a knee injury that would likely keep him out for a bit.