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What gene constraint can and cannot say

Constraint is strong population evidence, but it is not a disease mechanism by itself.

A population signal

Constraint measures depletion of classes of variation relative to an expectation model. It can support dosage sensitivity or selection, but it does not identify a specific disease mechanism.

Context still matters

A constrained gene may be important across many tissues. Tissue and cell-state evidence helps determine whether that general importance is relevant to the phenotype under study.

Use it as one layer

Report constraint alongside inheritance, variant consequence, phenotype fit, and functional context. Avoid allowing one summary metric to dominate the full evidence graph.

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