{"id":"W7117692053","doi":"10.64898/2025.12.30.25343229","title":"Individuals whose phenotype deviates from genetic expectation defined by common variation are enriched for rare damaging variants in genes that cause rare disease","year":2025,"lang":"en","type":"article","venue":"medRxiv","topic":"Genetic Associations and Epidemiology","field":"Biochemistry, Genetics and Molecular Biology","cited_by":0,"is_retracted":false,"has_abstract":true,"ca_institutions":"Discovery Centre","funders":"","keywords":"Disease; Allele; Phenotype; Rare events; Rare disease; Gene; Context (archaeology); Genetic testing; Genetic variation; Missense mutation","routes":{"ca_aff":true,"ca_fund":false,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.001160674,0.0003141461,0.0004797749,0.0008185309,0.0005503019,0.0007736598,0.0003197823,0.0004651612,0.003045044],"category_scores_gemma":[0.004269614,0.0001373963,0.0005577395,0.0009430993,0.0006981429,0.0003007904,0.0008773308,0.0005855355,0.0002171161],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002378302,"about_ca_system_score_gemma":0.0002145055,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00270424,"about_ca_topic_score_gemma":0.003670184,"domain_scores_codex":[0.9989088,0.0002435005,0.00009970336,0.0004719678,0.0001693493,0.0001067324],"domain_scores_gemma":[0.9969523,0.001327559,0.001114898,0.0003312311,0.00009182566,0.0001821183],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"observational","study_design_gemma":"observational","study_design_scores_codex":[0.0006718903,0.00003339949,0.9602808,0.00007952386,0.0004663641,0.0007127334,0.0002345648,0.001358091,0.02745022,0.0004258223,0.0003741443,0.007912486],"study_design_scores_gemma":[0.00001795907,0.00008021013,0.991083,0.00001652328,0.0001389247,0.001041176,0.000144224,0.003618938,0.002566417,0.0008152818,0.0004656571,0.00001169436],"study_design_candidate":"observational","study_design_consensus":"observational","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9958066,0.0002072915,0.002832701,0.00009969695,0.000009209364,0.000005894792,0.0007129502,0.00003745995,0.0002881917],"genre_scores_gemma":[0.9985943,0.00003490324,0.0009661153,0.00004156944,0.000004533111,0.000004912886,0.0002368464,0.000008986472,0.0001078737],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.003045044,"threshold_uncertainty_score":0.01018673,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01735950786260644,"score_gpt":0.2734522952413822,"score_spread":0.2560927873787758,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}