POLG2 p.Ala48=
c.144G>A · VCV3686290
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.9 | GERP -2.3 |
| Overall | ||
| CADD | 4.981 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- POLG2
- Protein
- p.Ala48=
- Coding
- c.144G>A
- MANE Select
- NM_007215
- Type
- single nucleotide variant
- Location
- chr17:64496825 (GRCh38)
- Gene constraint
- LOEUF 1.156 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.73 · 38 PDB
- Residue 48
- the 'disordered' region
Similar variants
- POLG2 p.Ala209Ser Uncertain significance ★★ ⚠ same type
- POLG2 p.Ala9Val Uncertain significance ★★ ⚠ same type
- POLG2 p.Arg122Ser Uncertain significance ★★ same type
- POLG2 p.Arg284Gln Uncertain significance ★★ ⚠ same type
- POLG2 p.Cys16Ser Uncertain significance ★★ ⚠ same type
- POLG2 p.Glu123Lys Uncertain significance ★★ ⚠ same type
- POLG2 p.Gly103Val Uncertain significance ★★ ⚠ same type
- POLG2 p.Gly188Arg Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/polg2-p-ala48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown