POLH p.Pro513=
c.1539A>G · rs540684746 · VCV2898458
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0869%, eas)
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 0.61 | GERP -3.7, phastCons 0.002 |
| Overall | ||
| CADD | 1.475 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0869%
East Asian · 39/44,886 alleles
Filtering AF
0.0653%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0578%
Overall
0.0031%
50/1,614,026 alleles · ultra-rare
exomes 41/1,461,676 · genomes 9/152,350 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0869% | 1,151 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| European (non-Finnish) | 0.000763% | 131,115 |
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.Pro513=
- Coding
- c.1539A>G
- MANE Select
- NM_006502
- dbSNP
- rs540684746
- Type
- single nucleotide variant
- Location
- chr6:43613954 (GRCh38)
- Gene constraint
- LOEUF 0.846 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73 · 241 PDB
- Residue 513
- 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-pro513 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown