POLRMT p.Asp205=
c.615T>C · VCV4939507
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00452%, eas)
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 -0.73 | GERP -2.7 |
| Overall | ||
| CADD | 0.445 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00452%
East Asian · 2/44,214 alleles
Filtering AF
0.00075%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000281%
Overall
0.000636%
10/1,571,580 alleles · very rare
exomes 8/1,419,514 · genomes 2/152,066 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00452% | 22,107 |
| European (non-Finnish) | 0.000689% | 145,074 |
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.Asp205=
- Coding
- c.615T>C
- MANE Select
- NM_005035
- Type
- single nucleotide variant
- Location
- chr19:629747 (GRCh38)
- Gene constraint
- LOEUF 1.26 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.99 · 25 PDB
- Residue 205
- a UniProt-annotated variant site (in coxpd55)
Similar variants
- POLRMT p.Asp205Glu Likely benign ★ 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-asp205 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown