POLRMT p.Asp697=
c.2091C>T · rs371118165 · VCV2648857
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.35%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -3.9 |
| Overall | ||
| CADD | 0.821 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.35%
African / African-American · 252/72,056 alleles
Filtering AF
0.314%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.3%
Overall
0.0202%
305/1,507,430 alleles · rare
exomes 162/1,355,112 · genomes 143/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.35% | 286 |
| Middle Eastern | 0.119% | 843 |
| Remaining individualsnot grpmax-eligible | 0.0429% | 2,333 |
| Admixed American | 0.0317% | 3,152 |
| South Asian | 0.00126% | 79,436 |
| European (non-Finnish) | 0.000619% | 161,528 |
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.Asp697=
- Coding
- c.2091C>T
- MANE Select
- NM_005035
- dbSNP
- rs371118165
- Type
- single nucleotide variant
- Location
- chr19:621607 (GRCh38)
- Gene constraint
- LOEUF 1.26 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.99 · 25 PDB
- Residue 697
- a UniProt-annotated variant site (in coxpd55); an α-helix
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-asp697 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown