Is MTREX p.Gln786= (c.2358A>G) pathogenic?

MTREX p.Gln786= (c.2358A>G) is classified Benign in MTREX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-04). Low-frequency (popmax 1.17%, afr).

How common is MTREX p.Gln786= (c.2358A>G) in the general population?

MTREX p.Gln786= (c.2358A>G) is low-frequency (popmax 1.17%, afr) (gnomAD).

MTREX p.Gln786=

c.2358A>G · rs114771389 · VCV767998

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.17%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -3.2, phastCons 0.007
Overall
CADD	1.704	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.17% African / African-American · 876/74,998 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.08%

Overall 0.065% 1,049/1,613,528 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.17%	86
South Asian	0.0945%	1,058
Remaining individualsnot grpmax-eligible	0.0816%	1,225
Admixed American	0.045%	2,222
Middle Eastern	0.0165%	6,058
East Asian	0.00892%	11,205
European (non-Finnish)	0.000339%	294,917

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.Gln786=
Coding: c.2358A>G
MANE Select: NM_015360
dbSNP: rs114771389
Type: single nucleotide variant
Location: chr5:55400298 (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-gln786 (accessed [today's date]).

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