Smith, named inactive for the 49ers' game at Seattle on Sunday night, has started 185 consecutive regular-season games dating to his 2001 rookie season with Cincinnati.
The news comes as little surprise even though the 49ers listed Smith as questionable for the game, an indication he had a 50 percent chance of playing. Smith did not practice all week. He was not seen warming up Sunday.
There is no precedent for Smith's absence, so it's tough to say how much this hurts the 49ers' chances. I will be watching to see how well the Seahawks run the ball to the right side of the 49ers' defensive line; whether the 49ers' rotation on the line wears down as the game progresses; whether Aldon Smith has a tougher time pressuring the quarterback without Justin Smith occupying blockers to facilitate twists; and whether Aldon Smith spends more time lining up opposite Seahawks right tackle Breno Giacomini.
Receiver Mario Manningham is active, bolstering the position. That could be good for the 49ers as they face a Seahawks secondary without cornerbacks Brandon Browner, Marcus Trufant and Walter Thurmond.