Is TRMT5 p.Gln53= (c.159A>G) pathogenic?

TRMT5 p.Gln53= (c.159A>G) is classified Likely benign in TRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-30). Very rare (popmax 0.000508%, nfe).

How common is TRMT5 p.Gln53= (c.159A>G) in the general population?

TRMT5 p.Gln53= (c.159A>G) is very rare (popmax 0.000508%, nfe) (gnomAD).

TRMT5 p.Gln53=

c.159A>G · VCV4775105

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

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 0.37	GERP 0.65, phastCons 1
Overall
CADD	6.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,026 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,020 alleles · very rare exomes 4/1,461,876 · genomes 2/152,144 · joint denominator

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.Gln53=
Coding: c.159A>G
MANE Select: NM_020810
Type: single nucleotide variant
Location: chr14:60979739 (GRCh38)
Gene constraint: LOEUF 0.969 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50

Full TRMT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRMT5 p.Gln53Arg Uncertain significance ★ ⚠ same residue
TRMT5 p.Gln53Glu Uncertain significance ★ ⚠ same residue
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

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-gln53 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown