POLH p.Ala264=
c.792C>T · rs747879122 · VCV2876532
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000848%, nfe)
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 -0.49 | GERP -1.4, phastCons 0.04 |
| Overall | ||
| CADD | 6.506 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000848%
European (non-Finnish) · 10/1,179,156 alleles
Filtering AF
0.000429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000313%
Overall
0.00062%
10/1,613,096 alleles · very rare
exomes 10/1,460,864 · genomes 0/152,232 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- POLH
- Protein
- p.Ala264=
- Coding
- c.792C>T
- MANE Select
- NM_006502
- dbSNP
- rs747879122
- Type
- single nucleotide variant
- Location
- chr6:43603919 (GRCh38)
- Gene constraint
- LOEUF 0.846 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73 · 241 PDB
- Residue 264
- an α-helix
Similar variants
- POLH p.Ala264Val Uncertain significance ★★ ⚠ same residue
- POLH p.Ala264Pro Uncertain significance ★ ⚠ same residue
- 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
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-ala264 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown