Is MTR p.Arg802Ter (c.2404C>T) pathogenic?

MTR p.Arg802Ter (c.2404C>T) is classified Pathogenic/Likely pathogenic in MTR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-01). Ultra-rare (popmax 0.0117%, amr); Associated with methylcobalamin deficiency type cblG.

What condition is associated with MTR p.Arg802Ter (c.2404C>T)?

MTR p.Arg802Ter (c.2404C>T) is associated with methylcobalamin deficiency type cblG, neural tube defects, folate-sensitive (ClinVar).

How common is MTR p.Arg802Ter (c.2404C>T) in the general population?

MTR p.Arg802Ter (c.2404C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

How is Homocystinuria without methylmalonic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MTR p.Arg802Ter

c.2404C>T · rs138695265 · VCV1339164

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

methylcobalamin deficiency type cblG

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 22 of 33
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.53, phastCons 1
Overall
CADD	38.0	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 0.0117% Admixed American · 7/59,966 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00223% 36/1,613,440 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,933
Admixed Americangrpmax	0.0117%	8,567
Remaining individualsnot grpmax-eligible	0.0032%	31,225
East Asian	0.00223%	44,880
South Asian	0.0022%	45,521
European (non-Finnish)	0.00153%	65,534

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg802Ter
Coding: c.2404C>T
MANE Select: NM_000254
dbSNP: rs138695265
Type: single nucleotide variant
Location: chr1:236863553 (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 802: the b12-binding domain

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

Disease context

methylcobalamin deficiency type cblG — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neural tube defects, folate-sensitive

For Homocystinuria without methylmalonic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

MTR p.Arg802Gln Uncertain significance ★ ⚠ same residue
MTR c.1812+1G>A Likely pathogenic ★★ same condition
MTR c.2474-1G>C Pathogenic ★★ same condition
MTR c.2595-2A>G Likely pathogenic ★★ same condition
MTR c.340-166A>G Pathogenic/Likely pathogenic ★★ same condition
MTR c.609+1088G>A Pathogenic ★★ same condition
MTR c.866-2A>C Pathogenic/Likely pathogenic ★★ same condition
MTR p.Arg1147Ter 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-arg802ter (accessed [today's date]).

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