It was an issue that cropped up last year when Alex Smith was fumbling the ball a lot. The fumbling isn't a problem this year. The problem was less his hand size and more of being a rookie QB, thrown into the NFL, with zero offensive talent surrounding him. But the game has slowed down considerably for Smith this year, so the small hands issue has gone away.
He's only fumbled twice this year, and has been protected pretty decently, but this is a maintenance pass offense, with only middlin' at best YPG, YPA and one TD pass per game, and this is in an NFC West where no pass defense is in the top half of the league, made even worse by those defenses seeing only one decent NFC West pass offense, the Rams'.
They've won by managing game successfully against lesser teams. If they beat us, it will require a real step up. Yes, it could happen, but only if (a) they take a significant step up, and on the road, which hasn't been their strong suit, and (b) we give them a little bit of a hand with breakdowns on both sides of the ball.