TRMT1 p.Phe309=
c.927C>T · rs146661261 · VCV3046777
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0114%, eas)
Conditions
1
TRMT1-related disorder
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 -9.1 | GERP -3.1 |
| Overall | ||
| CADD | 1.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0114%
East Asian · 5/43,956 alleles
Filtering AF
0.00442%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00291%
Overall
0.00162%
26/1,601,922 alleles · ultra-rare
exomes 19/1,450,122 · genomes 7/151,800 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0114% | 8,791 |
| Admixed American | 0.00335% | 29,855 |
| African / African-American | 0.00268% | 37,271 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,690 |
| European (non-Finnish) | 0.00128% | 78,274 |
| South Asian | 0.0011% | 90,878 |
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.Phe309=
- Coding
- c.927C>T
- MANE Select
- NM_001136035
- dbSNP
- rs146661261
- Type
- single nucleotide variant
- Location
- chr19:13110250 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.68 · 1 PDB
- Residue 309
- the trm1 methyltransferase domain
Disease context
TRMT1-related disorder
Similar variants
- TRMT1 p.Arg390Ter Pathogenic/Likely pathogenic ★★ same condition
- TRMT1 p.Arg544= Likely benign same condition
- TRMT1 p.Tyr446= Likely benign same condition
- TRMT1 c.255-8_255-2delinsAG Likely pathogenic ★ same condition
- 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
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-phe309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown