Folklore

HPO Phenotype Matching for Gene and Variant Prioritization

Folklore compares the patient's selected Human Phenotype Ontology (HPO) terms with the phenotype profile associated with each gene that carries a candidate variant. Ontology relationships allow related concepts to match even when their labels are not identical.

The result is a phenotype match score from 0 to 100 and a phenotype-aware clinical tier. Variant Analysis owns the ACMG classification; Phenotype Matching uses that existing class during prioritization but does not rewrite it. The PP3/BP4 computational evidence path is documented separately under BayesDel_noAF score thresholds. Neither score establishes a diagnosis.

Analysis Flow

1

Prepare the phenotype profile

Select HPO terms directly or review terms proposed from clinical free text. Only confirmed, present findings should be submitted for matching.

2

Identify eligible variants

Folklore evaluates non-reference variants that have a gene-associated HPO profile from Variant Analysis.

3

Compare HPO profiles

Each valid patient term is compared with the HPO terms associated with the variant gene, including related terms in the ontology.

4

Prioritize variants

Phenotype similarity is considered together with ACMG class, functional impact, population frequency, ClinVar evidence, and inheritance context.

5

Review grouped results

Genes are ranked by their strongest result. Expand a gene to inspect its variants and the individual HPO term matches.

HPO Terms Are Required

If no patient HPO terms are provided, Folklore cannot run phenotype matching and returns no phenotype-ranked results. Add or confirm the clinical findings before starting this stage.

What the Results Show

Gene rank

Genes ordered by the best clinical priority result among their variants.

Clinical tier

Tier 1, Tier 2, IF, Tier 3, or Tier 4 for phenotype-aware triage.

Clinical priority score

A tier-coded score used to order results within the same clinical workflow.

HPO term matches

Patient terms and their strongest semantic match in the gene profile.

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