TRMT1 p.Ala494=
c.1482C>T · VCV4940947
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00196%, amr)
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 0.031 | GERP -2.3, phastCons 0.38 |
| Overall | ||
| CADD | 4.081 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00196%
Admixed American · 1/51,126 alleles
Filtering AF
0.00098%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000809%
Overall
0.00129%
20/1,553,148 alleles · very rare
exomes 18/1,400,990 · genomes 2/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00196% | 51,126 |
| European (non-Finnish) | 0.00157% | 63,758 |
| South Asian | 0.00119% | 84,384 |
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
- TRMT1
- Protein
- p.Ala494=
- Coding
- c.1482C>T
- MANE Select
- NM_001136035
- Type
- single nucleotide variant
- Location
- chr19:13107775 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.68 · 1 PDB
- Residue 494
- the trm1 methyltransferase domain
Similar variants
- TRMT1 p.Ala494Thr Uncertain significance ★ ⚠ same residue
- TRMT1 p.Arg390Ter Pathogenic/Likely pathogenic ★★ same type
- TRMT1 p.Arg512Ter Likely pathogenic ★★ same type
- TRMT1 p.Ala337Thr Uncertain significance ★★ ⚠ same type
- TRMT1 p.Ala343Val Uncertain significance ★★ ⚠ same type
- TRMT1 p.Arg195Trp Uncertain significance ★★ ⚠ same type
- TRMT1 p.Arg358His Uncertain significance ★★ ⚠ same type
- TRMT1 p.Arg410Cys 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/trmt1-p-ala494 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown