Is MMAB p.Pro243= (c.729A>G) pathogenic?

MMAB p.Pro243= (c.729A>G) is classified Likely benign in MMAB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-28). Very rare (popmax 0.00668%, afr); Associated with methylmalonic aciduria, cblB type.

What condition is associated with MMAB p.Pro243= (c.729A>G)?

MMAB p.Pro243= (c.729A>G) is associated with methylmalonic aciduria, cblB type (ClinVar).

How common is MMAB p.Pro243= (c.729A>G) in the general population?

MMAB p.Pro243= (c.729A>G) is very rare (popmax 0.00668%, afr) (gnomAD).

How is Vitamin B12-responsive methylmalonic acidemia inherited?

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

MMAB p.Pro243=

c.729A>G · rs750028609 · VCV2872149

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Conditions

methylmalonic aciduria, cblB type

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 -6.5	GERP -3.8
Overall
CADD	0.431	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,870 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000496% 8/1,612,304 alleles · very rare exomes 4/1,460,090 · genomes 4/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,974
European (non-Finnish)	0.000255%	392,824

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: MMAB
Protein: p.Pro243=
Coding: c.729A>G
MANE Select: NM_052845
dbSNP: rs750028609
Type: single nucleotide variant
Location: chr12:109557052 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.39 · 6 PDB

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

Disease context

methylmalonic aciduria, cblB type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Vitamin B12-responsive methylmalonic acidemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

MMAB c.197-1G>T Pathogenic ★★ same condition
MMAB c.290+1G>A Likely pathogenic ★★ same condition
MMAB c.291-1G>A Pathogenic ★★ same condition
MMAB c.349-1G>C Pathogenic/Likely pathogenic ★★ same condition
MMAB c.584+2T>C Likely pathogenic ★★ same condition
MMAB p.Arg186Gln Pathogenic/Likely pathogenic ★★ same condition
MMAB p.Arg186Pro Likely pathogenic ★★ same condition
MMAB p.Arg186Trp 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/mmab-p-pro243 (accessed [today's date]).

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