Real Madrid forward Gareth Bale has been left out of Wales' squad for World Cup qualifiers against Czech Republic and Estonia with a "serious" injury.
Bale has missed five Real games with what Wales boss Robert Page describes as a "significant" hamstring tear.
The 32-year-old had been due to win his 100th cap against the Czechs in Prague on Friday, 8 October.
Aaron Ramsey is in the squad after missing Wales' three September games, along with Huddersfield's Sorba Thomas.
Juventus midfielder Ramsey was on a long list of withdrawals from last month's squad for the friendly in Finland and qualifiers against Belarus and Estonia having suffered a thigh injury.
Page said Bale's injury was so bad he feared he may also be unavailable for Wales next round of qualification games in November, though he is now confident that will not be the case.
"You grade hamstring injuries from one to four and his is nearer the four, so it is quite a significant hamstring tear," said Page.
"We are in close contact with him to see how it is developing and how he is progressing with it. This camp has come too soon for him unfortunately.
"Originally it might have been even progressing to November's camp - that is the significance of the injury. But thankfully he is recovering better than we anticipated.
"We are pretty certain now he will be okay for that. But for any injury, you can plan as much as you want but you can never guarantee it."
Bale, Wales' all-time leading goalscorer, completed a hat-trick deep into added time to snatch a dramatic 3-2 win over Belarus before a frustrating goalless draw at home to group minnows Estonia in Cardiff three days later.
Page accepts his absence will be a major blow to qualification hopes as Wales have no real alternative to the former Tottenham player.
"No, and that is not being disrespectful to the other players," agreed Page. "We all know our worth as coaches, managers and players especially.
"Gareth is a very special player and will be missed but we cannot cry about it. We just have to get on with it and try to look in a positive frame of mind and fully focus on two tough games coming up.
"But he showed his worth in the last camp especially when I thought he was at another level. To get his hat-trick and the plaudits that went with that - he thoroughly deserved them."
Page is confident there will be no repeat of Ramsey's withdrawal from the September squad and revealed Wales will take extra care of the 30-year-old former Cardiff and Arsenal player.
After the Wales squad announcement, Juventus revealed Ramsey would miss their Champions League tie at Chelsea on Thursday, 29 September with Italian media reporting his absence is due to muscle fatigue.
Adam Davies, who was forced to pull out of the previous squad after testing positive for Covid-19, returns along with Cardiff striker Kieffer Moore, who also missed the three games as a close contact of the Stoke City goalkeeper.
Page is also boosted by the return from injury of Ethan Ampadu, Neco Williams and David Brooks, while Connor Roberts could play for the first time since Euro 2020.
The former Swansea City defender has yet to feature for Burnley having undergone groin surgery before his transfer deadline-day move to the Premier League club.
There is a first call-up for Terriers winger Thomas, who only joined the Championship side from National League Boreham Wood earlier this year.
English-born Thomas, 22, qualifies for Wales via his mother from Newport.
"I have been made aware of Sorba in recent months and [we] obviously did our research and due diligence, had a look at him," said Page.
"I have been to watch him personally a couple of times and he deservedly got a call-up.
"It did not go to plan for him as a young lad. He was at West Ham's academy and got released and he went non-league, so was not afraid to drop down a couple of levels to go again.
"He deserves an enormous amount of credit for that, to go to Boreham Wood and have four or five seasons there and play really well, then Huddersfield take him.
"He dipped in and out of the Championship the back end of last season but has absolutely hit the ground running this season.
"He is really making a name for himself and it will be nice to work with him and look at him closely."
Cardiff forward Mark Harris is in the squad having won his first cap as a substitute in the 3-2 win in Russia last month having been a late call-up to that squad.
There is no place for Swansea centre-back Ben Cabango even though he is available having missed last month's games due to Covid-19.
Wales sit third in their qualifying group for the 2022 Qatar World Cup, level on points with the Czechs but nine points behind leaders Belgium.
Their away qualifier against Estonia is on Monday, 11 October.
Wales squad: Wayne Hennessey, Daniel Ward, Adam Davies, Chris Gunter, Ben Davies, Connor Roberts, Chris Mepham, Joe Rodon, Tom Lockyer, Neco Williams, James Lawrence, Rhys Norrington-Davies, Aaron Ramsey, Joe Allen, Jonny Williams, Ethan Ampadu, Harry Wilson, David Brooks, Joe Morrell, Matthew Smith, Dylan Levitt, Daniel James, Kieffer Moore, Tyler Roberts, Brennan Johnson, Rubin Colwill, Mark Harris, Sorba Thomas.
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