TRMT1 p.Ala468=
c.1404C>T · rs183961432 · VCV714024
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.66%, 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 0.077 | GERP 1, phastCons 0.65 |
| Overall | ||
| CADD | 9.163 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.66%
Admixed American · 845/50,986 alleles
Filtering AF
1.56%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.53%
Overall
0.059%
916/1,551,558 alleles · low-frequency
exomes 637/1,399,322 · genomes 279/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 1.66% | 60 |
| Remaining individualsnot grpmax-eligible | 0.0765% | 1,307 |
| African / African-American | 0.0273% | 3,657 |
| South Asian | 0.00119% | 84,048 |
| European (non-Finnish) | 0.000349% | 286,719 |
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.Ala468=
- Coding
- c.1404C>T
- MANE Select
- NM_001136035
- dbSNP
- rs183961432
- Type
- single nucleotide variant
- Location
- chr19:13107853 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.68 · 1 PDB
- Residue 468
- 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-ala468 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown