POLRMT p.Cys705=
c.2115C>T · VCV4939497
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.345%, sas)
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 -5.1 | GERP -3.5 |
| Overall | ||
| CADD | 3.777 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.345%
South Asian · 258/74,780 alleles
Filtering AF
0.31%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.297%
Overall
0.0265%
391/1,474,790 alleles · rare
exomes 362/1,322,468 · genomes 29/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.345% | 290 |
| Ashkenazi Jewishnot grpmax-eligible | 0.158% | 634 |
| Remaining individualsnot grpmax-eligible | 0.0527% | 1,899 |
| Middle Eastern | 0.0244% | 4,098 |
| Admixed American | 0.0141% | 7,075 |
| East Asian | 0.00511% | 19,580 |
| European (non-Finnish) | 0.00475% | 21,062 |
| African / African-American | 0.00284% | 35,169 |
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.Cys705=
- Coding
- c.2115C>T
- MANE Select
- NM_005035
- Type
- single nucleotide variant
- Location
- chr19:621583 (GRCh38)
- Gene constraint
- LOEUF 1.26 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.99 · 25 PDB
- Residue 705
- 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-cys705 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown