It's why Tomlin didn't give Clark the option.
The Steelers (12-4) will begin their quest for a second straight AFC title without Clark, who will be held out of the lineup as a precaution due to a sickle-cell trait that becomes aggravated when playing at higher elevations.
Tomlin and Clark met Monday to discuss the situation, with Tomlin telling the team's leading tackler he can travel but not suit up.
"Looking at data and all the variables he is at more risk, so we're not going to play him," Tomlin said. "It's just that simple."
Clark nearly died in 2007 when the condition first presented itself, losing his spleen and gall bladder in addition to losing 30 pounds. He was cleared by team doctors to play in Denver during Pittsburgh's last trip out west in 2009 before Tomlin intervened.
Tomlin did the same this time around, pointing to the inherent dangers involved and the capability of backup Ryan Mundy.
Clark did not speak to reporters on Tuesday but thanked fans for their concern through his Twitter account.
"I will not be playing. Glad that it's out now. So no more questions to ask," Clark tweeted.
Clark's teammates urged the 10-year veteran to sit out, with defensive end Brett Keisel and linebacker James Farrior both insisting the game isn't more important than Clark's life.
Mundy, who has two career starts on his resume, will get the call in place of Clark. The former West Virginia star has played well in spot duty and collected his first career interception in a win at Kansas City in late November.
"In a nutshell, he's starter capable," Tomlin said.
Yet Tomlin remains wary, pointing to Tebow's ability to come through in pressure situations, but believes Mundy can be effective with Clark watching in street clothes.
Isaac Redman and rookie John Clay will get the first crack at replacing Mendenhall. Veteran Mewelde Moore could be available as he recovers from a sprained left knee but Tomlin wouldn't speculate on if he would use Moore - a third-down back - in a feature role.
"We'll etch out a division of labor as we get closer," Tomlin said. "We like the group."
Tomlin isn't concerned about Redman's two fumbles against the Browns, miscues that allowed Cleveland to hang around until the final seconds. Clay received all nine of his carries in the fourth quarter, but Tomlin said that had more to do with giving Redman a breather.
Though Roethlisberger passed the ball 40 times against Cleveland and was sacked twice Tomlin believes the ankle is "certainly no worse" while adding he's "not concerned about (Roethlisberger's) overall physical state" though the quarterback may be limited in practice during the week.
Roethlisberger's numbers have taken a hit while playing basically on one leg. His passer rating over his last two starts is 62.1, down from 95.5 before getting hurt on Dec. 8.
Tomlin isn't exactly bothered by the downturn in Roethlisberger's efficiency.
"He won last week," Tomlin said, "That's how he's measured and that's how I'm measured."