Is MTREX p.Ile774Met (c.2322C>G) pathogenic?

MTREX p.Ile774Met (c.2322C>G) is classified Uncertain significance in MTREX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-09). AlphaMissense: likely benign (0.2328); Absent from gnomAD v4.1.

How common is MTREX p.Ile774Met (c.2322C>G) in the general population?

MTREX p.Ile774Met (c.2322C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTREX p.Ile774Met (c.2322C>G)?

AlphaMissense predicts likely benign (score 0.2328) — an in-silico prediction, not a clinical call.

MTREX p.Ile774Met

c.2322C>G · VCV3914445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2328 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2328	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -7.96	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 0.1	GERP -3.2, phastCons 0.98
Regional constraint	o/e 0.79	unconstrained · MANE · 66 kb · p 4.4e-07 · regional, not allelic
Overall
CADD	10.38	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

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: MTREX
Protein: p.Ile774Met
Coding: c.2322C>G
MANE Select: NM_015360
Type: single nucleotide variant
Location: chr5:55400262 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.68 · 11 PDB

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

Similar variants

MTREX p.Ala247Pro Uncertain significance ★ ⚠ same type
MTREX p.Ala93Thr Uncertain significance ★ ⚠ same type
MTREX p.Ala974Thr Uncertain significance ★ ⚠ same type
MTREX p.Arg128Gln Uncertain significance ★ ⚠ same type
MTREX p.Arg184Cys Uncertain significance ★ ⚠ same type
MTREX p.Arg290Gln Uncertain significance ★ ⚠ same type
MTREX p.Arg364Gln Uncertain significance ★ ⚠ same type
MTREX p.Arg364Trp 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/mtrex-p-ile774met (accessed [today's date]).

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