Autosomal dominant optic atrophy, classic type: genes and variants
Explore variant evidence for Autosomal dominant optic atrophy, classic type across 2 analyzed proteins (OPA1, PAX6). Linked ClinVar records include 13 pathogenic or likely pathogenic variants, 14 variants of uncertain significance and 14 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Autosomal dominant optic atrophy, classic type
OPA1: Dynamin-like GTPase OPA1, mitochondrial
A mitochondrial dynamin-related GTPase that fuses inner mitochondrial membranes and shapes cristae. By maintaining mitochondrial architecture and respiratory-chain function, it supports cell energy production, and OPA1 variants cause inherited optic-atrophy syndromes.
13 ClinVar pathogenic / likely pathogenic and 28 uncertain variants in OPA1 have source records linked to Autosomal dominant optic atrophy, classic type. Association strength is not clinical gene validity.
PAX6: Paired box protein Pax-6
It orchestrates developmental gene programs in the eye, forebrain, and pancreatic endocrine system. Haploinsufficiency most classically causes aniridia and can also produce broader ocular, endocrine, and neurodevelopmental abnormalities.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PAX6 have source records linked to Autosomal dominant optic atrophy, classic type. Association strength is not clinical gene validity.
Where Autosomal dominant optic atrophy, classic type variants cluster
- OPA1 Dynamin-type G (positions 285–561): 10 of 13 ClinVar pathogenic / likely pathogenic variants, 2.7× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Autosomal dominant optic atrophy, classic type
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| OPA1 D438G | 438 | Dynamin-type G | Pathogenic / likely pathogenic (★★) |
| OPA1 D438V | 438 | Dynamin-type G | Pathogenic / likely pathogenic (★★) |
| OPA1 D296H | 296 | Dynamin-type G | Pathogenic / likely pathogenic (★★) |
| OPA1 S545R | 545 | Dynamin-type G | Pathogenic / likely pathogenic (★★) |
| OPA1 S422R | 422 | Dynamin-type G | Pathogenic / likely pathogenic (★★) |
| OPA1 T449R | 449 | Dynamin-type G | Pathogenic / likely pathogenic (★★) |
| OPA1 L949P | 949 | Coiled coil | Pathogenic / likely pathogenic (★★) |
| OPA1 N430I | 430 | Dynamin-type G | Pathogenic / likely pathogenic (★) |
| OPA1 I432V | 432 | Dynamin-type G | Pathogenic / likely pathogenic (★) |
| OPA1 I433V | 433 | Dynamin-type G | Pathogenic / likely pathogenic (★) |
| OPA1 N240K | 240 | LQQQIQ motif | Pathogenic / likely pathogenic (★) |
| OPA1 V395M | 395 | Dynamin-type G | Pathogenic / likely pathogenic (★) |
| OPA1 K941T | 941 | Coiled coil | Pathogenic / likely pathogenic (★) |
Which prediction tools work for Autosomal dominant optic atrophy, classic type
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- AlphaMissense: 97 out of 100
- EVE: 92 out of 100
- CATVariant: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 85 out of 100
- MutPred2: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 77 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy also has ClinVar records linked to OPA1 variants; they fall mostly in different places as the Autosomal dominant optic atrophy, classic type variants (10 pathogenic / likely pathogenic).
- Optic atrophy also has ClinVar records linked to OPA1 variants; they fall mostly in different places as the Autosomal dominant optic atrophy, classic type variants (7 pathogenic / likely pathogenic).
Diseases related to Autosomal dominant optic atrophy, classic type
- Aniridia, also linked to PAX6
- Irido-corneo-trabecular dysgenesis, also linked to PAX6
- Auditory neuropathy, also linked to OPA1
- Optic atrophy, also linked to OPA1
- Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy, also linked to OPA1
- Coloboma, ocular, autosomal dominant, also linked to PAX6
- Foveal hypoplasia 1, also linked to PAX6
- Mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type), also linked to OPA1
Frequently asked questions
Which genes have records linked to Autosomal dominant optic atrophy, classic type?
This view contains 2 analyzed proteins: OPA1, PAX6. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 13 pathogenic or likely pathogenic variants, 14 variants of uncertain significance and 14 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 83 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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