Is TRMT5 p.Val265Phe (c.793G>T) pathogenic?

TRMT5 p.Val265Phe (c.793G>T) is classified Uncertain significance in TRMT5 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.5697); Very rare (popmax 0.00135%, afr); Associated with combined oxidative phosphorylation defect type 26.

What condition is associated with TRMT5 p.Val265Phe (c.793G>T)?

TRMT5 p.Val265Phe (c.793G>T) is associated with combined oxidative phosphorylation defect type 26 (ClinVar).

How common is TRMT5 p.Val265Phe (c.793G>T) in the general population?

TRMT5 p.Val265Phe (c.793G>T) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about TRMT5 p.Val265Phe (c.793G>T)?

AlphaMissense predicts likely pathogenic (score 0.5697) — an in-silico prediction, not a clinical call.

TRMT5 p.Val265Phe

Q: How is Combined oxidative phosphorylation defect type 26 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.793G>T · VCV4884808

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

combined oxidative phosphorylation defect type 26

Computational evidence

Protein change
AlphaMissense	0.5697	likely pathogenic
REVEL	0.442	indeterminate
SaProt	LLR -13.16	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.43	acceptor loss · deltas
Pangolin	Δ0.34	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 5,861 bp · p 0.27 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00135% African / African-American · 1/73,894 alleles

Overall 6.26e-05% 1/1,596,608 alleles · very rare exomes 1/1,444,360 · genomes 0/152,248 · 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.Val265Phe
Coding: c.793G>T
MANE Select: NM_020810
Type: single nucleotide variant
Location: chr14:60976126 (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

combined oxidative phosphorylation defect type 26 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined oxidative phosphorylation defect type 26 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

TRMT5 p.Arg291His Uncertain significance ★★ ⚠ same condition
TRMT5 p.Phe57Leu Uncertain significance ★★ ⚠ same condition
TRMT5 p.Pro311Ser Uncertain significance ★★ ⚠ same condition
TRMT5 p.Thr509= Uncertain significance ★★ same condition
TRMT5 p.Arg87Ter Likely pathogenic ★ same condition
TRMT5 p.Glu294Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
TRMT5 p.Ile222Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
TRMT5 p.Ile24Val Conflicting classifications of pathogenicity ★ ⚠ 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-val265phe (accessed [today's date]).

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