AlphaGenome MCP Server

Instructions

Implementation Reference

• scripts/alphagenome_bridge.py:323-350 (handler)

  Core handler function that executes the compare_variants tool logic by predicting effects for two variants using predict_variant_effect and comparing their impacts.

  def compare_variants(client, params: Dict[str, Any]) -> Dict[str, Any]:
      """
      Compare two variants side-by-side.
      """
      variant1 = params.get('variant1')
      variant2 = params.get('variant2')
  
      result1 = predict_variant_effect(client, variant1)
      result2 = predict_variant_effect(client, variant2)
  
      return {
          'variant1': {
              'id': result1['variant'],
              'impact': result1['interpretation']['impact_level'],
              'expression_fc': result1['predictions'].get('rna_seq', {}).get('fold_change', 0),
              'splice_delta': result1['predictions'].get('splice', {}).get('delta', 0)
          },
          'variant2': {
              'id': result2['variant'],
              'impact': result2['interpretation']['impact_level'],
              'expression_fc': result2['predictions'].get('rna_seq', {}).get('fold_change', 0),
              'splice_delta': result2['predictions'].get('splice', {}).get('delta', 0)
          },
          'comparison': {
              'more_severe': result1['variant'] if abs(result1['predictions'].get('rna_seq', {}).get('fold_change', 0)) > abs(result2['predictions'].get('rna_seq', {}).get('fold_change', 0)) else result2['variant']
          }
      }

• src/tools.ts:246-286 (schema)

  Input schema and metadata definition for the compare_variants tool, specifying structure for variant1 and variant2 inputs.

  export const COMPARE_VARIANTS_TOOL: Tool = {
    name: 'compare_variants',
    description: `Compare two variants side-by-side.
  
  Direct comparison of regulatory impacts between two variants.
  
  Returns:
  - Impact levels for both variants
  - Expression and splicing changes
  - Which variant is more severe
  
  Perfect for: comparing candidate variants, understanding relative severity.
  
  Example: "Compare rs429358 vs rs7412"`,
    inputSchema: {
      type: 'object',
      properties: {
        variant1: {
          type: 'object',
          properties: {
            chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
            position: { type: 'number', minimum: 1 },
            ref: { type: 'string', pattern: '^[ATGCatgc]+$' },
            alt: { type: 'string', pattern: '^[ATGCatgc]+$' },
          },
          required: ['chromosome', 'position', 'ref', 'alt'],
        },
        variant2: {
          type: 'object',
          properties: {
            chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
            position: { type: 'number', minimum: 1 },
            ref: { type: 'string', pattern: '^[ATGCatgc]+$' },
            alt: { type: 'string', pattern: '^[ATGCatgc]+$' },
          },
          required: ['chromosome', 'position', 'ref', 'alt'],
        },
      },
      required: ['variant1', 'variant2'],
    },
  };

• src/tools.ts:709-730 (registration)

  Registration of the compare_variants tool (COMPARE_VARIANTS_TOOL) in the ALL_TOOLS array, which is served via the MCP listTools endpoint.

  export const ALL_TOOLS: Tool[] = [
    PREDICT_VARIANT_TOOL,
    BATCH_SCORE_TOOL,
    ASSESS_PATHOGENICITY_TOOL,
    PREDICT_TISSUE_SPECIFIC_TOOL,
    COMPARE_VARIANTS_TOOL,
    PREDICT_SPLICE_IMPACT_TOOL,
    PREDICT_EXPRESSION_IMPACT_TOOL,
    ANALYZE_GWAS_LOCUS_TOOL,
    COMPARE_ALLELES_TOOL,
    BATCH_TISSUE_COMPARISON_TOOL,
    PREDICT_TF_BINDING_IMPACT_TOOL,
    PREDICT_CHROMATIN_IMPACT_TOOL,
    COMPARE_PROTECTIVE_RISK_TOOL,
    BATCH_PATHOGENICITY_FILTER_TOOL,
    COMPARE_VARIANTS_SAME_GENE_TOOL,
    PREDICT_ALLELE_SPECIFIC_EFFECTS_TOOL,
    ANNOTATE_REGULATORY_CONTEXT_TOOL,
    BATCH_MODALITY_SCREEN_TOOL,
    GENERATE_VARIANT_REPORT_TOOL,
    EXPLAIN_VARIANT_IMPACT_TOOL,
  ];

• src/index.ts:161-166 (handler)

  MCP server handler that dispatches compare_variants tool calls to the AlphaGenomeClient.

  case 'compare_variants': {
    const result = await getClient().compareVariants(args);
    return {
      content: [{ type: 'text', text: JSON.stringify(result, null, 2) }],
    };
  }

• src/alphagenome-client.ts:268-275 (helper)

  Client proxy method that invokes the Python bridge for compare_variants action.

  async compareVariants(params: any): Promise<any> {
    try {
      return await this.callPythonBridge('compare_variants', params);
    } catch (error) {
      if (error instanceof ApiError) throw error;
      throw new ApiError(`Variant comparison failed: ${error}`, 500);
    }
  }