Conciseness

Mostly efficient — tool parameters, formats, and cutoffs ("CADD PHRED ≥ 30", "REVEL ≥ 0.75", "AlphaMissense ≥ 0.564") earn their tokens — but the Pathogenicity Reasoning Framework spends several paragraphs on textbook genetics Claude already knows ("a variant in the DNA-binding domain of a transcription factor is more concerning than one in an unstructured linker", "homozygotes in gnomAD argue against full penetrance"), CADD thresholds are repeated in Phase 3, and generic boilerplate sections ("LOOK UP, DON'T GUESS", "COMPUTE, DON'T DESCRIBE") pad the budget. This fits anchor 3 (some unnecessary explanation, could be tightened) better than anchor 2, since the majority of the file is genuinely non-obvious tool guidance.

Actionability

Guidance is largely executable: exact input formats ("variant_id in the format chrom-pos-ref-alt (hg38, no 'chr' prefix)"), a worked example ("FAVOR_annotate_variant(variant='19-44908822-C-T')"), ready annotator strings ("clinvar,gnomad3,sift,polyphen2,revel,alphamissense,cadd_exome"), fallback chains, and a fill-in report template. It falls short of anchor 5 because several tools (ProtVar, ClinVar, ClinGen) get parameter descriptions but no complete example call covering the common case.

Workflow Clarity

Phases 0–5 are clearly sequenced with an overview diagram, explicit fallback chains for each tool failure ("gnomad_get_variant fails → use gnomad_search_variants by gene, or OpenCRAVAT gnomad3 annotator"), and a Data Gaps reporting checkpoint. Not anchor 5: there is no explicit validation that Phase 0 notation normalization succeeded before proceeding, and no verify/retry step on the synthesized report itself — minor checkpoint gaps, above anchor 3 because error-recovery loops are explicit.

Progressive Disclosure

The single ~230-line SKILL.md is well-sectioned but has no bundle files at all; per-tool parameter documentation, the report template, and the reasoning framework are all inlined where a references/ file per data source would keep the overview lean (e.g., the ProtVar/gnomAD/CADD parameter blocks). This matches anchor 3 — structure present, content that could be separate is inline — rather than anchor 4, which expects bulk detail appropriately split into mostly clear external references.

Specificity

The description enumerates multiple concrete capabilities: "ProtVar structural/functional context, ClinVar clinical classifications, gnomAD population frequencies, CADD deleteriousness, ClinGen gene-disease validity, plus FAVOR one-call comprehensive GRCh38 annotation" — a comprehensive, tool-specific action list, matching the level-5 anchor rather than level 4 (which requires minor coverage gaps).

Completeness

Both questions are answered explicitly: the "what" ("Functional annotation of protein variants — ProtVar structural/functional context... CADD deleteriousness...") and a direct "when" clause ("Use for variant annotation pipelines, missense effect prediction, and protein-level variant interpretation with functional context"), matching the anchor-5 example structure. It is not a 4 because the 'when' is explicit and specific rather than improvable.

Trigger Term Quality

"variant annotation pipelines, missense effect prediction, and protein-level variant interpretation" are natural user phrases, but common variations like "pathogenicity", "rsID", "HGVS", or "is this variant deleterious" are absent — good coverage with a few natural terms missing (anchor 4), not the synonym-complete coverage of anchor 5.

Distinctiveness Conflict Risk

The niche ("protein-level variant interpretation with functional context") and named tools (ProtVar, gnomAD, FAVOR) make it mostly distinct, but it shares ClinVar/ClinGen clinical vocabulary with a likely sibling variant-interpretation skill and the description itself does not state the boundary the body draws ("does NOT produce full ACMG classifications"), leaving minor overlap risk — anchor 4, not the minimal-conflict clarity of anchor 5.