Alpers syndrome: genes and variants
Explore variant evidence for Alpers syndrome across 1 analyzed protein (POLG). Linked ClinVar records include 26 pathogenic or likely pathogenic variants, 33 variants of uncertain significance and 20 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 Alpers syndrome
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.
26 ClinVar pathogenic / likely pathogenic and 53 uncertain variants in POLG have source records linked to Alpers syndrome. Association strength is not clinical gene validity.
Where Alpers syndrome variants cluster
- POLG Pol B (positions 943–958): 3 of 26 ClinVar pathogenic / likely pathogenic variants, 8.9× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Alpers syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| POLG A957V | 957 | Pol B | Pathogenic / likely pathogenic (★★) |
| POLG A957P | 957 | Pol B | Pathogenic / likely pathogenic (★★) |
| POLG R807P | 807 | Pathogenic / likely pathogenic (★★) | |
| POLG T851A | 851 | Pathogenic / likely pathogenic (★★) | |
| POLG A862T | 862 | Trigger loop | Pathogenic / likely pathogenic (★★) |
| POLG R869Q | 869 | Pathogenic / likely pathogenic (★★) | |
| POLG H932Y | 932 | Pathogenic / likely pathogenic (★★) | |
| POLG Y955C | 955 | Pol B | Pathogenic / likely pathogenic (★★) |
| POLG H1134Y | 1134 | Pol C | Pathogenic / likely pathogenic (★★) |
| POLG G426S | 426 | Pathogenic / likely pathogenic (★★) | |
| POLG G737R | 737 | Pathogenic / likely pathogenic (★★) | |
| POLG R853Q | 853 | Pathogenic / likely pathogenic (★★) | |
| POLG T914P | 914 | Pathogenic / likely pathogenic (★★) | |
| POLG P1073L | 1073 | Pathogenic / likely pathogenic (★★) | |
| POLG N864S | 864 | Trigger loop | Pathogenic / likely pathogenic (★★) |
| POLG V1106A | 1106 | Pathogenic / likely pathogenic (★★) | |
| POLG R227W | 227 | Pathogenic / likely pathogenic (★★) | |
| POLG R232H | 232 | Pathogenic / likely pathogenic (★★) | |
| POLG R627W | 627 | Pathogenic / likely pathogenic (★★) | |
| POLG W748S | 748 | Pathogenic / likely pathogenic (★★) | |
| POLG G1051R | 1051 | Pathogenic / likely pathogenic (★★) | |
| POLG R1096G | 1096 | Pathogenic / likely pathogenic (★★) | |
| POLG L244P | 244 | Pathogenic / likely pathogenic (★★) | |
| POLG Q308H | 308 | Pathogenic / likely pathogenic (★) | |
| POLG M919V | 919 | Pathogenic / likely pathogenic (★) | |
| POLG A467T | 467 | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Alpers syndrome
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| POLG R853W | 853 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R853Q at the same position is pathogenic; REVEL 0.881 |
Which prediction tools work for Alpers syndrome
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 100 out of 100
- PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 95 out of 100
- SIFT: 94 out of 100
Same protein, different disease
- Progressive sclerosing poliodystrophy also has ClinVar records linked to POLG variants; they fall partly in the same places as the Alpers syndrome variants (77 pathogenic / likely pathogenic).
- Progressive external ophthalmoplegia with mitochondrial DNA deletions also has ClinVar records linked to POLG variants; they fall mostly in different places as the Alpers syndrome variants (17 pathogenic / likely pathogenic).
- Mitochondrial disease also has ClinVar records linked to POLG variants; they fall partly in the same places as the Alpers syndrome variants (6 pathogenic / likely pathogenic).
Diseases related to Alpers syndrome
- Progressive sclerosing poliodystrophy, also linked to POLG
- Fanconi anemia complementation group J, also linked to POLG
- Fanconi anemia, also linked to POLG
- Progressive external ophthalmoplegia with mitochondrial DNA deletions, also linked to POLG
- Mitochondrial disease, also linked to POLG
- Sensory ataxic neuropathy - dysarthria - ophthalmoparesis, also linked to POLG
- Possible mitochondrial disorder - nuclear genes, also linked to POLG
- Mitochondrial DNA maintenance disorder, also linked to POLG
Frequently asked questions
Which genes have records linked to Alpers syndrome?
This view contains 1 analyzed proteins: POLG. 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 26 pathogenic or likely pathogenic variants, 33 variants of uncertain significance and 20 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. 1 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 126 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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