ACMG/AMP variant classification framework in arginase 1 deficiency: Implications for birth prevalence estimates and diagnostics
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Purpose: variant classification. Here, we incorporate American College of Medical Genetics and Genomics/Association for Molecular Pathology-developed guidelines for interpreting gene variants and in silico predictions to select allele frequencies for estimation of global birth prevalence of ARG1 deficiency. Methods: = 302). American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines were applied to classify variants using Franklin Genoox artificial intelligence-powered platform and manual review. Results: variants, 3 classified as pathogenic, 28 likely pathogenic, and 229 variant of uncertain significance. Mutant allele frequency estimates ranged from 17 to 266 per 100,000 and birth prevalence from 1 in 141,331 to 34,602,076. Conclusion: variants lack adequate evidence of pathogenicity. These findings underscore the significance of functional studies and accumulating clinical data for determination of variant pathogenicity and for improved understanding of global birth prevalence of ARG1 deficiency.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it