Is MMUT p.Pro41= (c.123A>G) pathogenic?

MMUT p.Pro41= (c.123A>G) is classified Likely benign in MMUT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-11). Very rare (popmax 0.00801%, afr); Associated with methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency.

What condition is associated with MMUT p.Pro41= (c.123A>G)?

MMUT p.Pro41= (c.123A>G) is associated with methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (ClinVar).

How common is MMUT p.Pro41= (c.123A>G) in the general population?

MMUT p.Pro41= (c.123A>G) is very rare (popmax 0.00801%, afr) (gnomAD).

MMUT p.Pro41=

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

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

c.123A>G · rs753769272 · VCV1110497

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.15	GERP -0.56, phastCons 0.75
Overall
CADD	8.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,882 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000434% 7/1,613,966 alleles · very rare exomes 3/1,461,788 · genomes 4/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,480
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Pro41=
Coding: c.123A>G
MANE Select: NM_000255
dbSNP: rs753769272
Type: single nucleotide variant
Location: chr6:49459344 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.72 · 6 PDB
Residue 41: an α-helix; a UniProt-annotated variant site (in mamm; mut-)

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 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
MMUT c.1957-2A>G 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-pro41 (accessed [today's date]).

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