TRMT1 p.Pro518=
c.1554A>G · rs148858467 · VCV781879
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.822%, nfe)
Conditions
1
Inborn genetic diseases
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 -14 | GERP -2.3 |
| Overall | ||
| CADD | 0.094 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.822%
European (non-Finnish) · 9,679/1,176,954 alleles
Filtering AF
0.809%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.803%
Overall
0.664%
10,677/1,608,314 alleles · rare
exomes 9,841/1,455,968 · genomes 836/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.822% | 122 |
| Remaining individualsnot grpmax-eligible | 0.494% | 202 |
| Finnishnot grpmax-eligible | 0.459% | 218 |
| Admixed American | 0.443% | 226 |
| Ashkenazi Jewishnot grpmax-eligible | 0.177% | 564 |
| African / African-American | 0.1% | 999 |
| Middle Eastern | 0.0496% | 2,017 |
| South Asian | 0.00334% | 29,966 |
| East Asian | 0.00223% | 44,814 |
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.Pro518=
- Coding
- c.1554A>G
- MANE Select
- NM_001136035
- dbSNP
- rs148858467
- Type
- single nucleotide variant
- Location
- chr19:13107603 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.68 · 1 PDB
Similar variants
- TRMT1 p.Ala337Thr Uncertain significance ★★ ⚠ same condition
- TRMT1 p.Ala343Val Uncertain significance ★★ ⚠ same condition
- TRMT1 p.Arg358His Uncertain significance ★★ ⚠ same condition
- TRMT1 p.Arg410Cys Uncertain significance ★★ ⚠ same condition
- TRMT1 p.Asp449Asn Uncertain significance ★★ ⚠ same condition
- TRMT1 p.Gly352Arg Uncertain significance ★★ ⚠ same condition
- TRMT1 p.Gly42Glu Uncertain significance ★★ ⚠ same condition
- TRMT1 p.Leu463Arg Uncertain significance ★★ ⚠ same condition
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-pro518 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown