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This monogram describes a pattern of p16INK4A variants with potential to associate with esophageal squamous cell carcinoma in a high risk ethnic population from Kashmir, India. A novel frame shifting deletion mutation that brings about premature transcript termination has been characterized. The monogram also describes the functional implications associated with this founder mutation which may have a significant impact in contributing to the genesis of esophageal squamous cell carcinoma, in addition of its significant diagnostic relevance.