Manningham is listed as questionable with a knee injury. He practiced in full all week.
The Michigan product has 27 catches for 323 yards and two touchdowns in seven games this season.
Running back Ahmad Bradshaw will miss a second consecutive game with a foot injury.
The Giants lead the NFC East with a 6-2 mark, while the 49ers hold the top spot in the NFC West with a 7-1 record.