Is MTR p.Asp783= (c.2349C>T) pathogenic?

MTR p.Asp783= (c.2349C>T) is classified Benign/Likely benign in MTR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). Rare (popmax 0.752%, afr); Associated with methylcobalamin deficiency type cblG.

What condition is associated with MTR p.Asp783= (c.2349C>T)?

MTR p.Asp783= (c.2349C>T) is associated with methylcobalamin deficiency type cblG (ClinVar).

How common is MTR p.Asp783= (c.2349C>T) in the general population?

MTR p.Asp783= (c.2349C>T) is rare (popmax 0.752%, afr) (gnomAD).

How is Homocystinuria without methylmalonic aciduria inherited?

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

MTR p.Asp783=

c.2349C>T · rs150734119 · VCV506534

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.752%, afr)

Conditions

methylcobalamin deficiency type cblG

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 -9.9	GERP -3.2
Overall
CADD	2.805	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.752% African / African-American · 564/75,046 alleles

Filtering AF 0.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.68%

Overall 0.0445% 718/1,614,052 alleles · rare exomes 341/1,461,722 · genomes 377/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.752%	133
Admixed American	0.1%	1,000
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.08%	1,250
South Asian	0.00329%	30,363
European (non-Finnish)	0.00305%	32,777

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.Asp783=
Coding: c.2349C>T
MANE Select: NM_000254
dbSNP: rs150734119
Type: single nucleotide variant
Location: chr1:236863498 (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 783: a binding site; 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

For Homocystinuria without methylmalonic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

MTR p.Asp783Asn 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-asp783 (accessed [today's date]).

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