TRMT1 p.Ala333=
c.999C>T · VCV3388105
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.186%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 0.39, phastCons 1 |
| Overall | ||
| CADD | 15.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.186%
European (non-Finnish) · 2,196/1,180,008 alleles
Filtering AF
0.18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.177%
Overall
0.148%
2,386/1,612,338 alleles · rare
exomes 2,237/1,460,002 · genomes 149/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.186% | 537 |
| Finnishnot grpmax-eligible | 0.164% | 609 |
| Remaining individualsnot grpmax-eligible | 0.0882% | 1,134 |
| African / African-American | 0.0227% | 4,412 |
| Admixed American | 0.0183% | 5,456 |
| East Asian | 0.00223% | 44,882 |
| South Asian | 0.0011% | 91,010 |
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.Ala333=
- Coding
- c.999C>T
- MANE Select
- NM_001136035
- Type
- single nucleotide variant
- Location
- chr19:13110178 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.68 · 1 PDB
- Residue 333
- the trm1 methyltransferase domain
Similar variants
- 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
- TRMT1 p.Asp449Asn 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-ala333 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown