Is MMAB p.Arg191Trp (c.571C>T) pathogenic?

MMAB p.Arg191Trp (c.571C>T) is classified Pathogenic in MMAB (ClinVar, Multiple submitters, 14 submitters; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.5916); Ultra-rare (popmax 0.01%, afr); Associated with Inborn genetic diseases.

What condition is associated with MMAB p.Arg191Trp (c.571C>T)?

MMAB p.Arg191Trp (c.571C>T) is associated with Inborn genetic diseases, methylmalonic aciduria, cblB type (ClinVar).

How common is MMAB p.Arg191Trp (c.571C>T) in the general population?

MMAB p.Arg191Trp (c.571C>T) is ultra-rare (popmax 0.01%, afr) (gnomAD).

What do computational predictors say about MMAB p.Arg191Trp (c.571C>T)?

AlphaMissense predicts likely pathogenic (score 0.5916) — an in-silico prediction, not a clinical call.

MMAB p.Arg191Trp

c.571C>T · rs376128990 · VCV218324

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely pathogenic

0.5916 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5916	likely pathogenic ✓ concordant with ClinVar
REVEL	0.924	moderately pathogenic-leaning
SaProt	LLR -12.45	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 4.2	GERP 0.84, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.26 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.01% African / African-American · 7/69,968 alleles

Filtering AF 0.00465% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00326%

Overall 0.00126% 19/1,510,268 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.01%	9,995
Remaining individualsnot grpmax-eligible	0.00358%	27,931
European (non-Finnish)	0.000895%	111,734

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.Arg191Trp
Coding: c.571C>T
MANE Select: NM_052845
dbSNP: rs376128990
Type: single nucleotide variant
Location: chr12:109561053 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: methylmalonic aciduria, cblB type

Similar variants

MMAB p.Arg191Gln Pathogenic ★★ ⚠ same residue
MMAB p.Arg191Gly Likely pathogenic ★ same residue
MMAB p.Arg191Pro 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-arg191trp (accessed [today's date]).

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