POLR2B p.Ala559=
c.1677A>C · rs371810125 · VCV2654777
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0284%, amr)
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 0.95 | GERP 0.84, phastCons 0.99 |
| Overall | ||
| CADD | 10.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0284%
Admixed American · 17/59,900 alleles
Filtering AF
0.018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.017%
Overall
0.0166%
267/1,609,538 alleles · ultra-rare
exomes 247/1,457,182 · genomes 20/152,356 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0284% | 3,524 |
| Remaining individualsnot grpmax-eligible | 0.0257% | 3,896 |
| European (non-Finnish) | 0.0199% | 5,028 |
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
- POLR2B
- Protein
- p.Ala559=
- Coding
- c.1677A>C
- MANE Select
- NM_000938
- dbSNP
- rs371810125
- Type
- single nucleotide variant
- Location
- chr4:57010876 (GRCh38)
- Gene constraint
- LOEUF 0.568 · pLI 0.24 (gnomAD)
- Structure
- AlphaFold pLDDT 90.01 · 22 PDB
- Residue 559
- an α-helix
Similar variants
- POLR2B p.Ala308Gly Uncertain significance ★ same type
- POLR2B p.Ala560Val Uncertain significance ★ ⚠ same type
- POLR2B p.Ala62Thr Uncertain significance ★ ⚠ same type
- POLR2B p.Ala74Val Uncertain significance ★ ⚠ same type
- POLR2B p.Arg1141Cys Uncertain significance ★ ⚠ same type
- POLR2B p.Arg1141His Uncertain significance ★ ⚠ same type
- POLR2B p.Arg157Gln Uncertain significance ★ ⚠ same type
- POLR2B p.Arg157Trp 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/polr2b-p-ala559 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown