POLRMT p.Pro742=
c.2226C>T · rs565088113 · VCV2648856
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.111%, afr)
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 -11 | GERP -3.5 |
| Overall | ||
| CADD | 0.124 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.111%
African / African-American · 72/64,876 alleles
Filtering AF
0.0903%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0828%
Overall
0.00665%
91/1,368,436 alleles · rare
exomes 37/1,216,798 · genomes 54/151,638 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.111% | 901 |
| Middle Eastern | 0.0544% | 1,839 |
| Admixed American | 0.0226% | 4,422 |
| Remaining individualsnot grpmax-eligible | 0.0173% | 5,791 |
| South Asian | 0.00168% | 59,660 |
| European (non-Finnish) | 9.36e-05% | 1,068,486 |
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.Pro742=
- Coding
- c.2226C>T
- MANE Select
- NM_005035
- dbSNP
- rs565088113
- Type
- single nucleotide variant
- Location
- chr19:621472 (GRCh38)
- Gene constraint
- LOEUF 1.26 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.99 · 25 PDB
- Residue 742
- a UniProt-annotated variant site (in coxpd55); a UniProt-annotated variant site (in coxpd55; results in decreased transcription of mitochondrial dna in vitro); the 'disordered' region
Similar variants
- POLRMT p.Pro742_Pro747del Conflicting classifications of pathogenicity ★ 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-pro742 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown