Variant evidence review
Review population evidence without treating frequency as a universal cutoff
Population evidence can support benign or pathogenic interpretations, but it must be evaluated against disease prevalence, penetrance, inheritance, ancestry representation and data quality. A frequency observation is evidence, not a diagnosis.
Agent question
What population observations are returned for this variant, and which ACMG/AMP criteria are actually applied?
Keep observation and criterion separate
Report the returned allele-frequency evidence, cohort and source version separately from any applied BA1, BS1 or PM2 criterion. Do not manufacture a criterion when the result reports only an observation or when population evidence is unavailable.
Review context
Population thresholds may require gene-specific or disease-specific calibration. BA1 also has recognized exceptions.
- Population and ancestry representation
- Allele count, number and coverage where returned
- Disease prevalence and penetrance assumptions
- Inheritance model
- Gene-specific specifications and recognized exceptions
- Source version and retrieval date
Public references
Clinical and data boundary
Folklore Clinical Variant Interpretation MCP is published by Helena Bioinformatics. It accepts public variant-level queries only, not patient, phenotype, family, segregation or private case data. Its results are automated decision support for qualified professional review, not a diagnosis or treatment recommendation.