POLR1C p.Pro30=
c.90C>T · rs888334484 · VCV1568377
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.028 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.34 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -6.2 | GERP -3.1 |
| Overall | ||
| CADD | 8.763 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,014 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000342%
5/1,461,860 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 75,014 |
| European (non-Finnish) | 0.000339% | 294,997 |
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
- POLR1C
- Protein
- p.Pro30=
- Coding
- c.90C>T
- MANE Select
- NM_203290
- dbSNP
- rs888334484
- Type
- single nucleotide variant
- Location
- chr6:43517326 (GRCh38)
- Gene constraint
- LOEUF 1.261 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.24 · 36 PDB
Similar variants
- POLR1C p.Pro30Ser Pathogenic/Likely pathogenic ★★ same residue
- POLR1C p.Pro30Ala Uncertain significance ★★ ⚠ same residue
- POLR1C c.70-1G>A Pathogenic/Likely pathogenic ★★ same type
- POLR1C c.70-2A>G Likely pathogenic ★★ same type
- POLR1C p.Arg109Cys Pathogenic/Likely pathogenic ★★ same type
- POLR1C p.Arg109His Pathogenic/Likely pathogenic ★★ same type
- POLR1C p.Arg279Gln Pathogenic/Likely pathogenic ★★ same type
- POLR1C p.Arg279Trp Pathogenic/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/polr1c-p-pro30 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown