TRMT1 p.Ala211=
c.633A>C · rs376673169 · VCV2649369
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.258%, sas)
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 -1.9 | GERP -2.9 |
| Overall | ||
| CADD | 7.983 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.258%
South Asian · 234/90,870 alleles
Filtering AF
0.23%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.22%
Overall
0.0151%
243/1,611,542 alleles · rare
exomes 231/1,459,262 · genomes 12/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.258% | 388 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,934 |
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.Ala211=
- Coding
- c.633A>C
- MANE Select
- NM_001136035
- dbSNP
- rs376673169
- Type
- single nucleotide variant
- Location
- chr19:13115287 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.68 · 1 PDB
- Residue 211
- the trm1 methyltransferase domain
Similar variants
- TRMT1 p.Ala211Ser 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-ala211 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown