POLR1C p.Pro244=
c.732C>T · rs748345433 · VCV2162600
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, 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 -13 | GERP -3.1 |
| Overall | ||
| CADD | 1.627 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,998 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.00062%
10/1,613,970 alleles · very rare
exomes 8/1,461,836 · genomes 2/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,999 |
| African / African-American | 0.00134% | 74,892 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 0.000424% | 235,999 |
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.Pro244=
- Coding
- c.732C>T
- MANE Select
- NM_203290
- dbSNP
- rs748345433
- Type
- single nucleotide variant
- Location
- chr6:43520701 (GRCh38)
- Gene constraint
- LOEUF 1.261 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.24 · 36 PDB
- Residue 244
- an α-helix
Similar variants
- POLR1C p.Pro244Ser 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
- POLR1C p.Arg77Ter 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-pro244 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown