Is MMAB p.Arg136= (c.408G>A) pathogenic?

MMAB p.Arg136= (c.408G>A) is classified Likely benign in MMAB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-08). Very rare (popmax 0.00224%, eas); Associated with methylmalonic aciduria, cblB type.

What condition is associated with MMAB p.Arg136= (c.408G>A)?

MMAB p.Arg136= (c.408G>A) is associated with methylmalonic aciduria, cblB type (ClinVar).

How common is MMAB p.Arg136= (c.408G>A) in the general population?

MMAB p.Arg136= (c.408G>A) is very rare (popmax 0.00224%, eas) (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.Arg136=

c.408G>A · rs760995089 · VCV1138460

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

methylmalonic aciduria, cblB type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.81	GERP -1.5, phastCons 1
Overall
CADD	8.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,726 alleles

Overall 6.87e-05% 1/1,456,586 alleles · very rare

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.Arg136=
Coding: c.408G>A
MANE Select: NM_052845
dbSNP: rs760995089
Type: single nucleotide variant
Location: chr12:109561793 (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 p.Arg136Gln Uncertain significance ★★ ⚠ same residue
MMAB p.Arg136Trp Uncertain significance ★ ⚠ same residue
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

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-arg136 (accessed [today's date]).

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