Is TRMT5 p.Ala45Val (c.134C>T) pathogenic?

TRMT5 p.Ala45Val (c.134C>T) is classified Uncertain significance in TRMT5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0728); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with TRMT5 p.Ala45Val (c.134C>T)?

TRMT5 p.Ala45Val (c.134C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRMT5 p.Ala45Val (c.134C>T) in the general population?

TRMT5 p.Ala45Val (c.134C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about TRMT5 p.Ala45Val (c.134C>T)?

AlphaMissense predicts likely benign (score 0.0728) — an in-silico prediction, not a clinical call.

TRMT5 p.Ala45Val

c.134C>T · rs142413701 · VCV2055110

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0728 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0728	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.73	GERP -3
Regional constraint	o/e 0.95	unconstrained · MANE · 5,861 bp · p 0.27 · regional, not allelic
Overall
CADD	1.894	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0113%

Overall 0.0113% 182/1,613,958 alleles · ultra-rare exomes 171/1,461,860 · genomes 11/152,098 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.0137%	7,284
South Asian	0.00878%	11,384
Remaining individualsnot grpmax-eligible	0.008%	12,501
East Asian	0.00446%	22,440
African / African-American	0.004%	24,989
Admixed American	0.00167%	59,998

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.Ala45Val
Coding: c.134C>T
MANE Select: NM_020810
dbSNP: rs142413701
Type: single nucleotide variant
Location: chr14:60979764 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRMT5 p.Ala45Thr Uncertain significance ★★ ⚠ same residue
TRMT5 p.Ala45= Likely benign ★ same residue
TRMT5 p.Ala188Asp Uncertain significance ★★ ⚠ same condition
TRMT5 p.Arg120Cys Uncertain significance ★★ ⚠ same condition
TRMT5 p.Arg125His Uncertain significance ★★ ⚠ same condition
TRMT5 p.Arg15Thr Uncertain significance ★★ ⚠ same condition
TRMT5 p.Arg266Gln Uncertain significance ★★ ⚠ same condition
TRMT5 p.His179Asp 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/trmt5-p-ala45val (accessed [today's date]).

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