POLRMT p.Pro183=
c.549C>T · VCV4939508
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.075%, nfe)
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 -6.8 | GERP -2.5 |
| Overall | ||
| CADD | 0.414 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.075%
European (non-Finnish) · 876/1,168,184 alleles
Filtering AF
0.0708%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0691%
Overall
0.0584%
928/1,587,962 alleles · ultra-rare
exomes 872/1,435,788 · genomes 56/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.075% | 1,334 |
| Remaining individualsnot grpmax-eligible | 0.0574% | 1,742 |
| Admixed American | 0.0106% | 9,455 |
| African / African-American | 0.00676% | 14,789 |
| South Asian | 0.00453% | 22,083 |
| East Asian | 0.00225% | 44,478 |
| Finnishnot grpmax-eligible | 0.00162% | 61,672 |
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
- POLRMT
- Protein
- p.Pro183=
- Coding
- c.549C>T
- MANE Select
- NM_005035
- Type
- single nucleotide variant
- Location
- chr19:629813 (GRCh38)
- Gene constraint
- LOEUF 1.26 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.99 · 25 PDB
- Residue 183
- a UniProt-annotated variant site (in coxpd55)
Similar variants
- POLRMT p.Gln681Ter Pathogenic/Likely pathogenic ★★ same type
- POLRMT p.Ala409Val Uncertain significance ★★ ⚠ same type
- POLRMT p.Ala444Val Uncertain significance ★★ ⚠ same type
- POLRMT p.Arg165Trp Uncertain significance ★★ ⚠ same type
- POLRMT p.Arg447Gln Uncertain significance ★★ ⚠ same type
- POLRMT p.Arg481Trp Uncertain significance ★★ ⚠ same type
- POLRMT p.Arg759His Uncertain significance ★★ ⚠ same type
- POLRMT p.Arg90Gln 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/polrmt-p-pro183 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown