Progressive external ophthalmoplegia with mitochondrial DNA deletions: genes and variants
Progressive external ophthalmoplegia with mitochondrial DNA deletions is linked to 1 analyzed protein (POLG). 17 DNA variants are known to cause it; 64 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1
Genes linked to Progressive external ophthalmoplegia with mitochondrial DNA deletions
POLG: DNA polymerase subunit gamma-1
It replicates and repairs mitochondrial DNA and is therefore essential for maintaining mitochondrial genome copy number and integrity. Pathogenic variants cause a broad spectrum including Alpers syndrome, progressive external ophthalmoplegia, epilepsy, ataxia, neuropathy, and liver disease.
17 disease-causing and 64 uncertain variants in POLG are linked to Progressive external ophthalmoplegia with mitochondrial DNA deletions.
Known disease-causing variants in Progressive external ophthalmoplegia with mitochondrial DNA deletions
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| POLG R807H | 807 | Disease-causing (★★) | |
| POLG R807C | 807 | Disease-causing (★★) | |
| POLG R869Q | 869 | Disease-causing (★★) | |
| POLG H932Y | 932 | Disease-causing (★★) | |
| POLG R597W | 597 | Disease-causing (★★) | |
| POLG P648R | 648 | Disease-causing (★★) | |
| POLG G737R | 737 | Disease-causing (★★) | |
| POLG G848S | 848 | Disease-causing (★★) | |
| POLG R852C | 852 | Disease-causing (★★) | |
| POLG L966R | 966 | Disease-causing (★★) | |
| POLG R275Q | 275 | Exo II | Disease-causing (★★) |
| POLG R309C | 309 | Disease-causing (★★) | |
| POLG N864S | 864 | Trigger loop | Disease-causing (★★) |
| POLG G763R | 763 | Disease-causing (★) | |
| POLG D890A | 890 | Pol A | Disease-causing (★) |
| POLG R3P | 3 | Disease-causing | |
| POLG S511N | 511 | Accessory-interacting determinant | Disease-causing |
Which prediction tools work for Progressive external ophthalmoplegia with mitochondrial DNA deletions
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 100 out of 100
- REVEL: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 96 out of 100
- phyloP: 95 out of 100
Same protein, different disease
- Progressive sclerosing poliodystrophy is also caused by POLG variants; they fall mostly in different places as the Progressive external ophthalmoplegia with mitochondrial DNA deletions variants (77 disease-causing).
- Mitochondrial DNA depletion syndrome is also caused by POLG variants; they fall mostly in different places as the Progressive external ophthalmoplegia with mitochondrial DNA deletions variants (26 disease-causing).
- Mitochondrial disease is also caused by POLG variants; they fall mostly in different places as the Progressive external ophthalmoplegia with mitochondrial DNA deletions variants (6 disease-causing).
- Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis is also caused by POLG variants; they fall mostly in different places as the Progressive external ophthalmoplegia with mitochondrial DNA deletions variants (6 disease-causing).
Diseases related to Progressive external ophthalmoplegia with mitochondrial DNA deletions
- Hereditary spastic paraplegia, also linked to POLG
- Progressive sclerosing poliodystrophy, also linked to POLG
- Mitochondrial DNA depletion syndrome, also linked to POLG
- Fanconi anemia, also linked to POLG
- Mitochondrial disease, also linked to POLG
- Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, also linked to POLG
- Possible mitochondrial disorder - nuclear genes, also linked to POLG
- Mitochondrial DNA maintenance disorder, also linked to POLG
- Mitochondrial neurogastrointestinal encephalomyopathy, also linked to POLG
Frequently asked questions
Which genes are linked to Progressive external ophthalmoplegia with mitochondrial DNA deletions?
In CATVariant, Progressive external ophthalmoplegia with mitochondrial DNA deletions is linked to 1 analyzed protein: POLG (DNA polymerase subunit gamma-1).
How many genetic variants are linked to Progressive external ophthalmoplegia with mitochondrial DNA deletions?
105 variants: 17 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 64 are of uncertain significance or have conflicting reports.
Which uncertain variants in Progressive external ophthalmoplegia with mitochondrial DNA deletions look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Progressive external ophthalmoplegia with mitochondrial DNA deletions?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 15 disease-causing and 16 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center