Is MTR p.Arg43= (c.129G>T) pathogenic?

MTR p.Arg43= (c.129G>T) is classified Likely benign in MTR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-18). Rare (popmax 0.197%, mid); Associated with MTR-related disorder.

What condition is associated with MTR p.Arg43= (c.129G>T)?

MTR p.Arg43= (c.129G>T) is associated with MTR-related disorder (ClinVar).

How common is MTR p.Arg43= (c.129G>T) in the general population?

MTR p.Arg43= (c.129G>T) is rare (popmax 0.197%, mid) (gnomAD).

MTR p.Arg43=

c.129G>T · rs138229278 · VCV3045511

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.197%, mid)

Conditions

MTR-related disorder

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 0.54	GERP -4
Overall
CADD	5.003	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.197% Middle Eastern · 12/6,082 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0892%

Overall 0.00781% 126/1,614,030 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.197%	507
Admixed American	0.0333%	2,999
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.00686%	14,568
South Asian	0.00549%	18,218
African / African-American	0.00267%	37,463

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: MTR
Protein: p.Arg43=
Coding: c.129G>T
MANE Select: NM_000254
dbSNP: rs138229278
Type: single nucleotide variant
Location: chr1:236803522 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.60 · 9 PDB
Residue 43: the hcy-binding domain; an α-helix

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

Disease context

MTR-related disorder

Similar variants

MTR p.Arg43Gln Uncertain significance ★★ ⚠ same residue
MTR p.Arg43Trp Uncertain significance ★★ ⚠ same residue
MTR p.Pro1173Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
MTR p.Arg43Leu Uncertain significance ★★ same residue
MTR p.Asp825Gly Likely pathogenic ★ same condition
MTR p.Trp975Ter Likely pathogenic ★ same condition
MTR c.2044-9C>G Likely benign same condition
MTR p.Asp1119fs Likely pathogenic ★ same condition

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/mtr-p-arg43 (accessed [today's date]).

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