Is TRMT5 p.Phe352Leu (c.1054T>C) pathogenic?

TRMT5 p.Phe352Leu (c.1054T>C) is classified Uncertain significance in TRMT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.8919); Absent from gnomAD v4.1.

How common is TRMT5 p.Phe352Leu (c.1054T>C) in the general population?

TRMT5 p.Phe352Leu (c.1054T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRMT5 p.Phe352Leu (c.1054T>C)?

AlphaMissense predicts likely pathogenic (score 0.8919) — an in-silico prediction, not a clinical call.

TRMT5 p.Phe352Leu

c.1054T>C · rs2139640838 · VCV1298583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8919 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8919	likely pathogenic · top 8% in TRMT5
REVEL	0.326	indeterminate
SaProt	LLR -11.21	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 5,861 bp · p 0.27 · regional, not allelic
Overall
CADD	26.1	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.Phe352Leu
Coding: c.1054T>C
MANE Select: NM_020810
dbSNP: rs2139640838
Type: single nucleotide variant
Location: chr14:60975865 (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.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-phe352leu (accessed [today's date]).

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