POLR2E p.Pro53=
c.159G>A · rs75657655 · VCV768946
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 10.7%, afr) — too common for a highly-penetrant pathogenic allele
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 -20 | GERP -2.5 |
| Overall | ||
| CADD | 0.318 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.7%
African / African-American · 7,990/74,994 alleles
Filtering AF
10.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.4%
Overall
0.555%
8,959/1,613,710 alleles · common
exomes 4,400/1,461,400 · genomes 4,559/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.7% | 9 |
| Remaining individualsnot grpmax-eligible | 0.624% | 160 |
| Admixed American | 0.612% | 163 |
| Middle Eastern | 0.248% | 404 |
| European (non-Finnish) | 0.0158% | 6,344 |
| South Asian | 0.0121% | 8,278 |
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
- POLR2E
- Protein
- p.Pro53=
- Coding
- c.159G>A
- MANE Select
- NM_002695
- dbSNP
- rs75657655
- Type
- single nucleotide variant
- Location
- chr19:1093977 (GRCh38)
- Gene constraint
- LOEUF 1.522 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.18 · 59 PDB
Similar variants
- POLR2E p.Arg101Gln Uncertain significance ★ ⚠ same type
- POLR2E p.Arg162Pro Uncertain significance ★ ⚠ same type
- POLR2E p.Arg181Cys Uncertain significance ★ ⚠ same type
- POLR2E p.Arg187His Uncertain significance ★ ⚠ same type
- POLR2E p.Arg24Cys Uncertain significance ★ ⚠ same type
- POLR2E p.Arg52Gln Uncertain significance ★ ⚠ same type
- POLR2E p.Asp120Asn Uncertain significance ★ ⚠ same type
- POLR2E p.Asp3Ala 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/polr2e-p-pro53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown