Is MMAB p.Ser50= (c.150G>A) pathogenic?

MMAB p.Ser50= (c.150G>A) is classified Conflicting classifications of pathogenicity in MMAB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-28). Ultra-rare (popmax 0.0307%, afr); Associated with methylmalonic aciduria, cblB type.

What condition is associated with MMAB p.Ser50= (c.150G>A)?

MMAB p.Ser50= (c.150G>A) is associated with methylmalonic aciduria, cblB type (ClinVar).

How common is MMAB p.Ser50= (c.150G>A) in the general population?

MMAB p.Ser50= (c.150G>A) is ultra-rare (popmax 0.0307%, 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.Ser50=

c.150G>A · rs754357121 · VCV706935

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Conditions

methylmalonic aciduria, cblB type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -1.9	GERP -1.8
Overall
CADD	6.944	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,900 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00341% 55/1,613,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,257
Remaining individualsnot grpmax-eligible	0.0096%	10,413
East Asian	0.00223%	44,896
European (non-Finnish)	0.00212%	47,199

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.Ser50=
Coding: c.150G>A
MANE Select: NM_052845
dbSNP: rs754357121
Type: single nucleotide variant
Location: chr12:109571695 (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 50: the 'disordered' region

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.Ser50Leu 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
MMAB p.Arg186Pro 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-ser50 (accessed [today's date]).

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