POLH p.Pro316=
c.948C>G · VCV3688842
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 0.62 | GERP 0.83, phastCons 1 |
| Overall | ||
| CADD | 8.316 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,070 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000124%
2/1,614,016 alleles · very rare
exomes 2/1,461,748 · genomes 0/152,268 · 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.Pro316=
- Coding
- c.948C>G
- MANE Select
- NM_006502
- Type
- single nucleotide variant
- Location
- chr6:43604678 (GRCh38)
- Gene constraint
- LOEUF 0.846 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73 · 241 PDB
Similar variants
- POLH p.Pro316Arg 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
- POLH p.Thr191Pro 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-pro316 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown