Is MMAB p.Arg191Pro (c.572G>C) pathogenic?

MMAB p.Arg191Pro (c.572G>C) is classified Likely pathogenic in MMAB (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9713); Absent from gnomAD v4.1; Associated with methylmalonic aciduria, cblB type.

What condition is associated with MMAB p.Arg191Pro (c.572G>C)?

MMAB p.Arg191Pro (c.572G>C) is associated with methylmalonic aciduria, cblB type (ClinVar).

How common is MMAB p.Arg191Pro (c.572G>C) in the general population?

MMAB p.Arg191Pro (c.572G>C) is absent from gnomAD v4.1 (gnomAD).

How is Vitamin B12-responsive methylmalonic acidemia inherited?

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

What do computational predictors say about MMAB p.Arg191Pro (c.572G>C)?

AlphaMissense predicts likely pathogenic (score 0.9713) — an in-silico prediction, not a clinical call.

MMAB p.Arg191Pro

c.572G>C · rs746219370 · VCV2501701

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9713 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

methylmalonic aciduria, cblB type

Computational evidence

Protein change
AlphaMissense	0.9713	likely pathogenic ✓ concordant with ClinVar · top 1% in MMAB
REVEL	0.97	strongly pathogenic-leaning
SaProt	LLR -15.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.26 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MMAB
Protein: p.Arg191Pro
Coding: c.572G>C
MANE Select: NM_052845
dbSNP: rs746219370
Type: single nucleotide variant
Location: chr12:109561052 (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 191: a UniProt-annotated variant site (in macb); 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.Arg191Gln Pathogenic ★★ ⚠ same residue
MMAB p.Arg191Trp Pathogenic ★★ same residue
MMAB p.Arg191Gly Likely pathogenic ★ same residue
MMAB p.Arg191= Likely benign ★ same residue
MMAB p.Arg191dup Likely pathogenic ★★ same residue
MMAB p.Arg191fs Likely pathogenic ★ same residue
MMAB c.197-1G>T Pathogenic ★★ same condition
MMAB c.290+1G>A 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-arg191pro (accessed [today's date]).

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