feat(01-01): create Python package scaffold with config system

- pyproject.toml: installable package with bioinformatics dependencies
- Pydantic config schema with validation (ensembl_release >= 100, directory creation)
- YAML config loader with override support
- Default config with Ensembl 113, gnomAD v4.1
- 5 passing tests for config validation and hashing

tests/test_config.py

@@ -0,0 +1,135 @@
+"""Tests for configuration loading and validation."""
+
+from pathlib import Path
+
+import pytest
+from pydantic import ValidationError
+
+from usher_pipeline.config import load_config, load_config_with_overrides
+from usher_pipeline.config.schema import PipelineConfig
+
+
+def test_load_valid_config():
+    """Test loading valid default configuration."""
+    config = load_config("config/default.yaml")
+
+    assert isinstance(config, PipelineConfig)
+    assert config.versions.ensembl_release == 113
+    assert config.versions.gnomad_version == "v4.1"
+    assert config.api.rate_limit_per_second == 5
+    assert config.api.max_retries == 5
+    assert config.scoring.gnomad == 0.20
+
+
+def test_invalid_config_missing_field(tmp_path):
+    """Test that missing required field raises ValidationError."""
+    invalid_config = tmp_path / "invalid.yaml"
+    invalid_config.write_text("""
+versions:
+  ensembl_release: 113
+api:
+  rate_limit_per_second: 5
+scoring:
+  gnomad: 0.20
+""")
+
+    with pytest.raises(ValidationError) as exc_info:
+        load_config(invalid_config)
+
+    # Check that error mentions missing field
+    assert "data_dir" in str(exc_info.value)
+
+
+def test_invalid_ensembl_release(tmp_path):
+    """Test that ensembl_release < 100 raises ValidationError."""
+    invalid_config = tmp_path / "invalid_ensembl.yaml"
+    invalid_config.write_text("""
+data_dir: data
+cache_dir: data/cache
+duckdb_path: data/pipeline.duckdb
+versions:
+  ensembl_release: 99
+  gnomad_version: v4.1
+api:
+  rate_limit_per_second: 5
+  max_retries: 5
+  cache_ttl_seconds: 86400
+  timeout_seconds: 30
+scoring:
+  gnomad: 0.20
+  expression: 0.20
+  annotation: 0.15
+  localization: 0.15
+  animal_model: 0.15
+  literature: 0.15
+""")
+
+    with pytest.raises(ValidationError) as exc_info:
+        load_config(invalid_config)
+
+    # Check that error mentions ensembl_release constraint
+    error_str = str(exc_info.value)
+    assert "ensembl_release" in error_str
+    assert "greater than or equal to 100" in error_str.lower() or "100" in error_str
+
+
+def test_config_hash_deterministic():
+    """Test that config hash is deterministic and changes with config."""
+    config1 = load_config("config/default.yaml")
+    config2 = load_config("config/default.yaml")
+
+    # Same config should produce same hash
+    assert config1.config_hash() == config2.config_hash()
+
+    # Hash should be SHA-256 (64 hex chars)
+    assert len(config1.config_hash()) == 64
+
+    # Different config should produce different hash
+    config3 = load_config_with_overrides(
+        "config/default.yaml",
+        {"api.rate_limit_per_second": 10},
+    )
+    assert config3.config_hash() != config1.config_hash()
+
+
+def test_config_creates_directories(tmp_path):
+    """Test that loading config creates data and cache directories."""
+    config_file = tmp_path / "test_config.yaml"
+
+    # Use non-existent directories
+    data_dir = tmp_path / "test_data"
+    cache_dir = tmp_path / "test_cache"
+
+    config_file.write_text(f"""
+data_dir: {data_dir}
+cache_dir: {cache_dir}
+duckdb_path: {tmp_path / "test.duckdb"}
+versions:
+  ensembl_release: 113
+  gnomad_version: v4.1
+api:
+  rate_limit_per_second: 5
+  max_retries: 5
+  cache_ttl_seconds: 86400
+  timeout_seconds: 30
+scoring:
+  gnomad: 0.20
+  expression: 0.20
+  annotation: 0.15
+  localization: 0.15
+  animal_model: 0.15
+  literature: 0.15
+""")
+
+    # Directories should not exist before loading
+    assert not data_dir.exists()
+    assert not cache_dir.exists()
+
+    # Load config
+    config = load_config(config_file)
+
+    # Directories should be created
+    assert data_dir.exists()
+    assert cache_dir.exists()
+    assert data_dir.is_dir()
+    assert cache_dir.is_dir()