Is MTR p.Arg19Gln (c.56G>A) pathogenic?

MTR p.Arg19Gln (c.56G>A) is classified Likely benign in MTR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.0772); Ultra-rare (popmax 0.0111%, eas); Associated with Inborn genetic diseases.

What condition is associated with MTR p.Arg19Gln (c.56G>A)?

MTR p.Arg19Gln (c.56G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MTR p.Arg19Gln (c.56G>A) in the general population?

MTR p.Arg19Gln (c.56G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about MTR p.Arg19Gln (c.56G>A)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

MTR p.Arg19Gln

c.56G>A · rs767724201 · VCV2608352

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.6	GERP -3.2, phastCons 0.001
Regional constraint	o/e 0.81	unconstrained · MANE · 102 kb · p 9.3e-14 · regional, not allelic
Overall
CADD	9.037	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 0.0111% East Asian · 5/44,900 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000744% 12/1,613,952 alleles · ultra-rare exomes 11/1,461,806 · genomes 1/152,146 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,980
African / African-American	0.00267%	37,446
South Asian	0.0011%	91,084
European (non-Finnish)	0.000339%	295,001

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.Arg19Gln
Coding: c.56G>A
MANE Select: NM_000254
dbSNP: rs767724201
Type: single nucleotide variant
Location: chr1:236803449 (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 19: the hcy-binding domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTR p.Arg19Trp Uncertain significance ★ ⚠ same residue
MTR p.Ala205Val Uncertain significance ★★ same condition
MTR p.Ala442Glu Uncertain significance ★★ ⚠ same condition
MTR p.Arg1029Trp Uncertain significance ★★ ⚠ same condition
MTR p.Arg220Gln Uncertain significance ★★ ⚠ same condition
MTR p.Arg220Trp Uncertain significance ★★ ⚠ same condition
MTR p.Arg43Gln Uncertain significance ★★ ⚠ same condition
MTR p.Arg43Trp Uncertain significance ★★ ⚠ 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-arg19gln (accessed [today's date]).

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