Is MTR p.Asn150= (c.450T>C) pathogenic?

MTR p.Asn150= (c.450T>C) is classified Uncertain significance in MTR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00446%, eas); Associated with Disorders of Intracellular Cobalamin Metabolism.

What condition is associated with MTR p.Asn150= (c.450T>C)?

MTR p.Asn150= (c.450T>C) is associated with Disorders of Intracellular Cobalamin Metabolism (ClinVar).

How common is MTR p.Asn150= (c.450T>C) in the general population?

MTR p.Asn150= (c.450T>C) is very rare (popmax 0.00446%, eas) (gnomAD).

MTR p.Asn150=

c.450T>C · rs1661234823 · VCV876528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

Disorders of Intracellular Cobalamin Metabolism

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 -0.066	GERP -3.8, phastCons 0.86
Overall
CADD	5.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,860 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000137% 2/1,461,600 alleles · very rare

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.Asn150=
Coding: c.450T>C
MANE Select: NM_000254
dbSNP: rs1661234823
Type: single nucleotide variant
Location: chr1:236810543 (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 150: the hcy-binding domain

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

Disease context

Disorders of Intracellular Cobalamin Metabolism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTR c.*5537T>C Uncertain significance ★★ same condition
MTR p.Arg1167Gln Uncertain significance ★★ ⚠ same condition
MTR p.Glu672Lys Uncertain significance ★★ ⚠ same condition
MTR p.Phe363Leu Uncertain significance ★★ ⚠ same condition
MTR p.Pro148Leu Uncertain significance ★★ ⚠ same condition
MTR p.Pro749Ser Uncertain significance ★★ ⚠ same condition
MTR p.Thr954Met Uncertain significance ★★ ⚠ same condition
MTR c.1076-11C>T Benign/Likely benign ★★ 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-asn150 (accessed [today's date]).

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