{"enrichment":{"faq":[{"a":"tooluniverse-variant-functional-annotation integrates ProtVar, ClinVar, gnomAD, and CADD to deliver comprehensive annotation. For TP53 R175H, the skill maps the amino acid change to structural domains, retrieves conservation scores, pulls population frequencies from gnomAD, and surfaces clinical classifications from ClinVar. You get functional context\u2014domain location, predicted deleteriousness, and allele frequency\u2014in a single output, ideal for understanding how the missense change affects protein structure and function.","q":"How do I annotate a protein variant like TP53 R175H with tooluniverse-variant-functional-annotation?"},{"a":"tooluniverse-variant-functional-annotation combines ClinVar for clinical significance, gnomAD for population allele frequencies, CADD for deleteriousness scoring, and ProtVar for protein-level structural and functional annotation. This multi-source integration lets you assess variant pathogenicity using conservation, location, frequency, and prediction data without needing to query each resource separately.","q":"What databases does tooluniverse-variant-functional-annotation use?"},{"a":"Yes. tooluniverse-variant-functional-annotation annotates protein variants with structural and functional context, including whether the change falls within conserved domains. It combines conservation patterns with location data to help you understand the structural impact of missense variants and assess their likely functional consequence.","q":"Can tooluniverse-variant-functional-annotation check if a variant is in a conserved domain?"},{"a":"tooluniverse-variant-functional-annotation evaluates functional impact by combining multiple signals: conservation scores, domain location, CADD deleteriousness predictions, and clinical classifications from ClinVar. For missense variants, it maps the amino acid change to protein structure, shows whether it affects conserved regions, and retrieves population frequencies from gnomAD to contextualize rarity and predicted pathogenicity.","q":"What's the functional impact of a missense variant according to this skill?"},{"a":"tooluniverse-variant-functional-annotation queries gnomAD to retrieve population allele frequencies for your variant. These frequencies help assess variant rarity and are a key input for pathogenicity assessment\u2014rare variants in conserved regions with high CADD scores are typically more likely to be deleterious than common variants.","q":"How does tooluniverse-variant-functional-annotation retrieve population frequencies?"},{"a":"No. tooluniverse-variant-functional-annotation is built for variant interpretation pipelines where you need functional evidence and structural context without full ACMG classification. It delivers protein-level annotation, conservation patterns, clinical classifications, and population frequencies\u2014use it to understand how a missense change affects protein structure and function, then apply your own classification rules.","q":"Is tooluniverse-variant-functional-annotation a full ACMG classification tool?"}],"shadow_tags":["protein-structure-mapping","pathogenicity-scoring","population-genetics","clinical-classification","multi-database-integration","missense-prediction","conservation-analysis","variant-normalization","evidence-grading","functional-genomics"],"summary_rewrite":"This skill combines multiple authoritative databases to deliver protein-level variant annotation, mapping structural domains, conservation patterns, clinical classifications, and population allele frequencies. It's built for variant interpretation pipelines where you need functional evidence without full ACMG classification\u2014use it to understand how a missense change affects protein structure and function."},"files":[{"bytes":13981,"path":"skills/tooluniverse-variant-functional-annotation/SKILL.md","sha256":"548196ce4e64dcbcfcb602ae62fa97615b697514f0bae27dc0455ee3ab698043","url":"https://skillfed.io/files/mims-harvard/ToolUniverse/tooluniverse-variant-functional-annotation/0b89d0cd/SKILL.md"}],"id":"mims-harvard/ToolUniverse/tooluniverse-variant-functional-annotation","links":{"html":"https://skillfed.io/mims-harvard/ToolUniverse/tooluniverse-variant-functional-annotation","md":"https://skillfed.io/mims-harvard/ToolUniverse/tooluniverse-variant-functional-annotation.md","repo":"https://github.com/mims-harvard/ToolUniverse"},"meta":{"agents_supported":[],"first_seen":"2026-07-28","forks":242,"language":"Python","last_updated":"2026-07-27","license":"Apache-2.0","name":"tooluniverse-variant-functional-annotation","publisher":"mims-harvard","stars":1595},"relations":{"similar":[{"id":"mims-harvard/ToolUniverse/tooluniverse-variant-interpretation"},{"id":"mims-harvard/ToolUniverse/tooluniverse-acmg-variant-classification"},{"id":"mims-harvard/ToolUniverse/tooluniverse-rare-disease-diagnosis"},{"id":"mims-harvard/ToolUniverse/tooluniverse-variant-analysis"},{"id":"mims-harvard/ToolUniverse/tooluniverse-variant-to-mechanism"},{"id":"jaechang-hits/SciAgent-Skills/snpeff-variant-annotation"},{"id":"mims-harvard/ToolUniverse/tooluniverse-structural-variant-analysis"},{"id":"K-Dense-AI/scientific-agent-skills/onekgpd"},{"id":"jaechang-hits/SciAgent-Skills/gnomad-database"},{"id":"Delphine-L/claude_global/gnomad"}]},"slug":{"owner":"mims-harvard","repo":"ToolUniverse","skill":"tooluniverse-variant-functional-annotation"},"version":"0b89d0cd"}