Is MMAB p.Arg190= (c.570C>T) pathogenic?

MMAB p.Arg190= (c.570C>T) is classified Likely benign in MMAB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-11). Very rare (popmax 8.57e-05%, nfe); Associated with methylmalonic aciduria, cblB type.

What condition is associated with MMAB p.Arg190= (c.570C>T)?

MMAB p.Arg190= (c.570C>T) is associated with methylmalonic aciduria, cblB type (ClinVar).

How common is MMAB p.Arg190= (c.570C>T) in the general population?

MMAB p.Arg190= (c.570C>T) is very rare (popmax 8.57e-05%, nfe) (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.Arg190=

c.570C>T · rs1448685745 · VCV2109305

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.57e-05%, nfe)

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 2.9	GERP 0.79, phastCons 1
Overall
CADD	7.396	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.57e-05% European (non-Finnish) · 1/1,167,312 alleles

Overall 6.94e-05% 1/1,440,720 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.Arg190=
Coding: c.570C>T
MANE Select: NM_052845
dbSNP: rs1448685745
Type: single nucleotide variant
Location: chr12:109561054 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.39 · 6 PDB
Residue 190: an α-helix; a binding site

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.Arg190Cys Pathogenic/Likely pathogenic ★★ same residue
MMAB p.Arg190His Pathogenic ★★ same residue
MMAB p.Arg190Leu Uncertain significance ★ ⚠ same residue
MMAB p.Arg190Gly Pathogenic ★ same residue
MMAB p.Arg190Pro 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

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-arg190 (accessed [today's date]).

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