POLG (DNA polymerase subunit gamma-1) variants and mutations

POLG (also known as DNA polymerase subunit gamma-1) is a human protein-coding gene encoding a DNA polymerase subunit gamma-1 protein. 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. This analysis covers 2,426 POLG variants and mutations. Of these, 71% have computational variant effect predictions. Disease context includes mitochondrial DNA depletion syndrome 4a, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, and progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal. Example POLG variants include S2N, R3C, and R3P.

Variant analysis overview

Gene: POLG
Protein: DNA polymerase subunit gamma-1
UniProt accession: P54098
Organism: Homo sapiens
Variants analyzed: 2426
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 2,295 unspecified-consequence records; 16 frameshift variants; 50 synonymous variants; 48 missense variants; 1 in-frame insertions; 3 splice-region variants; 2 stop-gained variants; 5 in-frame deletions; 6 substitution
Prediction scores: 1,723 variants have prediction scores (71% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: mitochondrial DNA depletion syndrome 4a, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal, mitochondrial neurogastrointestinal encephalomyopathy, Sensory ataxic neuropathy - dysarthria - ophthalmoparesis, Alpers syndrome, spinocerebellar ataxia with epilepsy, mitochondrial DNA depletion syndrome, autosomal dominant progressive external ophthalmoplegia, autosomal recessive progressive external ophthalmoplegia, mitochondrial disease, Fanconi anemia.

Protein structure and variant hotspots

Protein features: 25 binding sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable POLG variants

Examples include S2N, R3C, R3P, L4Q, L5F, W6*, W6S, R7G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

POLG analysis run — POLG (2,426 variants) — completed 2026-08-19