Is MTR p.Arg591Ter (c.1771C>T) pathogenic?

MTR p.Arg591Ter (c.1771C>T) is classified Pathogenic in MTR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-01). Very rare (popmax 0.00446%, eas).

How common is MTR p.Arg591Ter (c.1771C>T) in the general population?

MTR p.Arg591Ter (c.1771C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

MTR p.Arg591Ter

c.1771C>T · rs777459947 · VCV1331535

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 33
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.29	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00031% 5/1,613,842 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,442
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.000169%	589,977

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.Arg591Ter
Coding: c.1771C>T
MANE Select: NM_000254
dbSNP: rs777459947
Type: single nucleotide variant
Location: chr1:236852596 (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 591: a binding site; the pterin-binding domain; an α-helix

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

Similar variants

MTR c.1812+1G>A Likely pathogenic ★★ same type
MTR c.2474-1G>C Pathogenic ★★ same type
MTR c.2595-2A>G Likely pathogenic ★★ same type
MTR c.340-166A>G Pathogenic/Likely pathogenic ★★ same type
MTR c.609+1088G>A Pathogenic ★★ same type
MTR c.866-2A>C Pathogenic/Likely pathogenic ★★ same type
MTR p.Arg1147Ter Pathogenic ★★ same type
MTR p.Arg585Ter Pathogenic/Likely pathogenic ★★ 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/mtr-p-arg591ter (accessed [today's date]).

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