Is TRMT5 p.Pro311Ser (c.931C>T) pathogenic?

TRMT5 p.Pro311Ser (c.931C>T) is classified Uncertain significance in TRMT5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-13). AlphaMissense: likely pathogenic (0.7912); Absent from gnomAD v4.1; Associated with combined oxidative phosphorylation defect type 26.

What condition is associated with TRMT5 p.Pro311Ser (c.931C>T)?

TRMT5 p.Pro311Ser (c.931C>T) is associated with combined oxidative phosphorylation defect type 26 (ClinVar).

How common is TRMT5 p.Pro311Ser (c.931C>T) in the general population?

TRMT5 p.Pro311Ser (c.931C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRMT5 p.Pro311Ser (c.931C>T)?

AlphaMissense predicts likely pathogenic (score 0.7912) — an in-silico prediction, not a clinical call.

TRMT5 p.Pro311Ser

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.931C>T · VCV3810855

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7912 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

combined oxidative phosphorylation defect type 26

Computational evidence

Protein change
AlphaMissense	0.7912	likely pathogenic
REVEL	0.573	indeterminate
SaProt	LLR -14.26	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 5,861 bp · p 0.27 · regional, not allelic
Overall
CADD	27.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRMT5
Protein: p.Pro311Ser
Coding: c.931C>T
MANE Select: NM_020810
Type: single nucleotide variant
Location: chr14:60975988 (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.Pro311= Likely benign ★ same residue
TRMT5 p.Arg291His Uncertain significance ★★ ⚠ same condition
TRMT5 p.Phe57Leu 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-pro311ser (accessed [today's date]).

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