POLG p.Pro857Ser
c.2569C>T · VCV3898070
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4576 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4576 | ambiguous |
|---|---|---|
| REVEL | 0.738 | pathogenic-leaning |
| SaProt | LLR -10.08 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 1.04 | unconstrained · MANE · 13 kb · p 0.21 · regional, not allelic |
| Overall | ||
| CADD | 28.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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
- POLG
- Protein
- p.Pro857Ser
- Coding
- c.2569C>T
- MANE Select
- NM_002693
- Type
- single nucleotide variant
- Location
- chr15:89321765 (GRCh38)
- Gene constraint
- LOEUF 0.847 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.53 · 36 PDB
Similar variants
- POLG p.Pro857= Likely benign ★ same residue
- POLG c.3643+2T>C Pathogenic ★★★ same type
- POLG p.Ala1105Pro Likely pathogenic ★★★ same type
- POLG p.Arg1096Cys Likely pathogenic ★★★ same type
- POLG p.Asp1184Asn Pathogenic ★★★ same type
- POLG p.Gln1175Ter Likely pathogenic ★★★ same type
- POLG p.Lys1191Asn Likely pathogenic ★★★ same type
- POLG c.3483-14T>C 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/polg-p-pro857ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown