POLH p.Val266=
c.798C>A · rs2532465385 · VCV2709954
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 2.2 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 8.922 | 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
- POLH
- Protein
- p.Val266=
- Coding
- c.798C>A
- MANE Select
- NM_006502
- dbSNP
- rs2532465385
- Type
- single nucleotide variant
- Location
- chr6:43603925 (GRCh38)
- Gene constraint
- LOEUF 0.846 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73 · 241 PDB
- Residue 266
- a UniProt-annotated variant site (in xpv); an α-helix
Similar variants
- POLH c.764+1G>A Pathogenic/Likely pathogenic ★★ same type
- POLH p.Arg167Ter Pathogenic ★★ same type
- POLH p.Arg303Ter Pathogenic ★★ same type
- POLH p.Arg356Ter Pathogenic ★★ same type
- POLH p.Glu164Ter Pathogenic/Likely pathogenic ★★ same type
- POLH p.Ser213Ter Pathogenic/Likely pathogenic ★★ same type
- POLH p.Thr191Pro Likely pathogenic ★★ same type
- POLH c.272+4A>G 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/polh-p-val266 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown