POLRMT p.Ala558=
c.1674G>C · rs61746452 · VCV788335
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.504%, mid)
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 -10 | GERP -3.5 |
| Overall | ||
| CADD | 0.052 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.504%
Middle Eastern · 27/5,360 alleles
Filtering AF
0.392%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.374%
Overall
0.321%
5,021/1,561,788 alleles · rare
exomes 4,586/1,409,490 · genomes 435/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.504% | 199 |
| Admixed American | 0.438% | 229 |
| European (non-Finnish) | 0.379% | 264 |
| Remaining individualsnot grpmax-eligible | 0.334% | 299 |
| Ashkenazi Jewishnot grpmax-eligible | 0.313% | 320 |
| African / African-American | 0.061% | 1,639 |
| Finnishnot grpmax-eligible | 0.0516% | 1,938 |
| South Asian | 0.0117% | 8,538 |
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.Ala558=
- Coding
- c.1674G>C
- MANE Select
- NM_005035
- dbSNP
- rs61746452
- Type
- single nucleotide variant
- Location
- chr19:622326 (GRCh38)
- Gene constraint
- LOEUF 1.26 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.99 · 25 PDB
- Residue 558
- a UniProt-annotated variant site (in coxpd55); an α-helix
Similar variants
- POLRMT p.Ala558Thr Uncertain significance ★ ⚠ same residue
- 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
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-ala558 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown