Is MMUT p.Val682= (c.2046T>C) pathogenic?

MMUT p.Val682= (c.2046T>C) is classified Likely benign in MMUT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-04). Very rare (popmax 0.004%, afr); Associated with methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency.

What condition is associated with MMUT p.Val682= (c.2046T>C)?

MMUT p.Val682= (c.2046T>C) is associated with methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (ClinVar).

How common is MMUT p.Val682= (c.2046T>C) in the general population?

MMUT p.Val682= (c.2046T>C) is very rare (popmax 0.004%, afr) (gnomAD).

MMUT p.Val682=

Q: How is Vitamin B12-unresponsive methylmalonic acidemia inherited?

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

c.2046T>C · rs201456803 · VCV1143831

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency

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 1.4	phastCons 1
Overall
CADD	4.109	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,942 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,074 alleles · very rare exomes 1/1,461,836 · genomes 2/152,238 · joint denominator

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: MMUT
Protein: p.Val682=
Coding: c.2046T>C
MANE Select: NM_000255
dbSNP: rs201456803
Type: single nucleotide variant
Location: chr6:49435534 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.72 · 6 PDB
Residue 682: a UniProt-annotated variant site (in mamm; mut-); the b12-binding domain; an α-helix; a UniProt-annotated variant site (in mamm; mut0)

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

Disease context

methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Vitamin B12-unresponsive methylmalonic acidemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

MMUT p.Val682Ala Uncertain significance ★ ⚠ same residue
MMUT c.1084-10A>G Pathogenic/Likely pathogenic ★★ same condition
MMUT c.1084-2A>G Pathogenic/Likely pathogenic ★★ same condition
MMUT c.1445-2A>G Pathogenic/Likely pathogenic ★★ same condition
MMUT c.1560+1G>T Pathogenic ★★ same condition
MMUT c.1677-1G>A Pathogenic ★★ same condition
MMUT c.1677-1G>C Pathogenic/Likely pathogenic ★★ same condition
MMUT c.1956+2T>C Pathogenic/Likely 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/mmut-p-val682 (accessed [today's date]).

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