Is MTREX p.Arg184Cys (c.550C>T) pathogenic?

MTREX p.Arg184Cys (c.550C>T) is classified Uncertain significance in MTREX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely pathogenic (0.9932); Very rare (popmax 0.00549%, afr).

How common is MTREX p.Arg184Cys (c.550C>T) in the general population?

MTREX p.Arg184Cys (c.550C>T) is very rare (popmax 0.00549%, afr) (gnomAD).

What do computational predictors say about MTREX p.Arg184Cys (c.550C>T)?

AlphaMissense predicts likely pathogenic (score 0.9932) — an in-silico prediction, not a clinical call.

MTREX p.Arg184Cys

c.550C>T · VCV4112061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9932	likely pathogenic
REVEL	0.584	indeterminate
SaProt	LLR -15.63	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 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 16 kb · p 0.014 · 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 0.00549% African / African-American · 4/72,816 alleles

Filtering AF 0.004% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00367%

Overall 0.00414% 65/1,571,932 alleles · very rare exomes 58/1,419,676 · genomes 7/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00549%	18,204
European (non-Finnish)	0.00509%	19,662
Remaining individualsnot grpmax-eligible	0.0033%	30,267

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.Arg184Cys
Coding: c.550C>T
MANE Select: NM_015360
Type: single nucleotide variant
Location: chr5:55340044 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.68 · 11 PDB
Residue 184: the helicase atp-binding domain; a β-strand

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.Arg290Gln Uncertain significance ★ ⚠ same type
MTREX p.Arg364Gln Uncertain significance ★ ⚠ same type
MTREX p.Arg364Trp 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-arg184cys (accessed [today's date]).

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