POLH p.Glu705=
c.2115A>G · rs1172995001 · VCV2983725
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00424%, 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 2.3 | GERP 0.79, phastCons 1 |
| Overall | ||
| CADD | 7.339 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00424%
European (non-Finnish) · 50/1,180,020 alleles
Filtering AF
0.00326%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00294%
Overall
0.00316%
51/1,613,936 alleles · very rare
exomes 51/1,461,576 · genomes 0/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00424% | 23,600 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,492 |
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.Glu705=
- Coding
- c.2115A>G
- MANE Select
- NM_006502
- dbSNP
- rs1172995001
- Type
- single nucleotide variant
- Location
- chr6:43614530 (GRCh38)
- Gene constraint
- LOEUF 0.846 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73 · 241 PDB
- Residue 705
- the 'disordered' region
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-glu705 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown