CADD (Combined Annotation Dependent Depletion)

Overview

CADD (Combined Annotation Dependent Depletion) is a framework for scoring the deleteriousness of single nucleotide variants and small indels in the human genome. It integrates over 60 functional annotations using a support vector machine trained on simulated de novo variants versus fixed variants in the human lineage. CADD Phred-scaled scores ≥20 indicate the top 1% of deleterious variants; ≥30 indicates the top 0.1%.

Used by

  • Used to annotate functional impact of somatic variants in endometrial polyps; UBE2A p.(Arg6Trp) received a CADD score of 24.4, supporting its classification as a deleterious driver alteration PMID:28445112

Notes

  • Phred-scaled C-score ≥20 = top 1% most deleterious variants; ≥30 = top 0.1%.
  • Covers all possible SNVs genome-wide (pre-computed) and can score small indels.
  • Often used alongside REVEL, AlphaMissense, and population-frequency tools for comprehensive variant interpretation.

Sources

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