• SF is built to sustain drives. The 49ers convert 52.4% on third down (100th percentile).

• Indy’s defense has struggled to get off the field. Colts third-down stop rate is 54.9% (28th percentile).

• SF limits explosive passes. The 49ers allow explosive passes at 5.6% (86th percentile).

• Indy can give up chunk plays through the air. Colts “Expl Pass Allowed” sits at 7.7% (25th percentile).

• Colts QB injuries change the whole game. With Jones and Richardson on IR, expect a tighter playbook and more reliance on the run game.

• Key health swing: Colts LT Bernhard Raimann (Questionable) and CB Sauce Gardner (Questionable) can directly impact protection and coverage if they sit or are limited.

• 49ers -5.0 (-125): SF’s third-down edge (52.4% conversion) matches up well versus Indy’s weaker third-down defense (28th percentile stop rate).

• Under 47.0 (-127): QB uncertainty for Indy and a likely run-leaning plan can drain clock and cut down total plays.

• 49ers moneyline -300: The price reflects the QB gap. It is expensive, so it fits better in parlays than as a standalone bet.

• Colts team total Under 20.0 (-120): Indy needs efficiency to reach 20. With QB injuries, empty drives are a real risk.

• George Kittle Over 59.5 receiving yards (-122): Indy’s pass defense profile (25th percentile in explosive pass prevention) leaves room for a high-volume tight end day.

• Josh Downs Under 23.5 receiving yards (-116): SF’s explosive-pass defense is strong, and the Colts’ QB situation adds downside to a low yardage line.

This game starts with one simple question: can the Colts function on offense with their quarterback situation? If Indy cannot, it becomes a field-position and clock game fast.

San Francisco’s best on-paper edge is third down. A 52.4% conversion rate means longer drives and more chances to turn red-zone trips into points.

From a betting view, the market is already shading hard toward San Francisco. 49ers -5.0 makes sense if you think Indy’s offense stalls early. The Under 47.0 also fits if the Colts go run-heavy and protect their QB.

Props-wise, I’m looking at Kittle Over 59.5 as a clean matchup play, and I’m cautious with Colts pass-catchers because the QB floor is low. Odds move fast late in the week, so keep an eye on any quarterback confirmation before locking anything in.