Is MTREX p.Arg364Trp (c.1090C>T) pathogenic?

MTREX p.Arg364Trp (c.1090C>T) is classified Uncertain significance in MTREX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely pathogenic (0.8574); Ultra-rare (popmax 0.0159%, nfe).

How common is MTREX p.Arg364Trp (c.1090C>T) in the general population?

MTREX p.Arg364Trp (c.1090C>T) is ultra-rare (popmax 0.0159%, nfe) (gnomAD).

What do computational predictors say about MTREX p.Arg364Trp (c.1090C>T)?

AlphaMissense predicts likely pathogenic (score 0.8574) — an in-silico prediction, not a clinical call.

MTREX p.Arg364Trp

c.1090C>T · VCV3296760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8574 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8574	likely pathogenic
REVEL	0.28	benign-leaning
SaProt	LLR -10.42	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.72, phastCons 0.77
Regional constraint	o/e 0.85	unconstrained · MANE · 5,813 bp · p 0.098 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0159% European (non-Finnish) · 187/1,176,100 alleles

Filtering AF 0.014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0133%

Overall 0.0127% 204/1,608,892 alleles · ultra-rare exomes 194/1,457,070 · genomes 10/151,822 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0159%	6,289
South Asian	0.00771%	12,975
Remaining individualsnot grpmax-eligible	0.00642%	15,576
African / African-American	0.00402%	24,887
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,570
Admixed American	0.00335%	29,886

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: MTREX
Protein: p.Arg364Trp
Coding: c.1090C>T
MANE Select: NM_015360
Type: single nucleotide variant
Location: chr5:55345178 (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.Arg364Gln Uncertain significance ★ ⚠ same residue
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.Arg575Cys 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-arg364trp (accessed [today's date]).

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