TRMT5 p.Glu258=
c.774G>A · rs1160757022 · VCV1988167
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0175%, mid)
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 0.42 | GERP 0.4, phastCons 0.98 |
| Overall | ||
| CADD | 5.821 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0175%
Middle Eastern · 1/5,702 alleles
Filtering AF
0.000556%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000208%
Overall
0.000248%
4/1,610,060 alleles · ultra-rare
exomes 4/1,457,788 · genomes 0/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0175% | 5,702 |
| Admixed American | 0.00335% | 29,850 |
| East Asian | 0.00224% | 44,732 |
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
- TRMT5
- Protein
- p.Glu258=
- Coding
- c.774G>A
- MANE Select
- NM_020810
- dbSNP
- rs1160757022
- Type
- single nucleotide variant
- Location
- chr14:60977532 (GRCh38)
- Gene constraint
- LOEUF 0.969 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.50
Similar variants
- TRMT5 p.Ala188Asp Uncertain significance ★★ ⚠ same type
- TRMT5 p.Ala45Thr Uncertain significance ★★ ⚠ same type
- TRMT5 p.Ala45Val Uncertain significance ★★ ⚠ same type
- TRMT5 p.Arg120Cys Uncertain significance ★★ ⚠ same type
- TRMT5 p.Arg125His Uncertain significance ★★ ⚠ same type
- TRMT5 p.Arg15Thr Uncertain significance ★★ ⚠ same type
- TRMT5 p.Arg266Gln Uncertain significance ★★ ⚠ same type
- TRMT5 p.Arg291His 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/trmt5-p-glu258 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown