Is MMAB p.Ala207= (c.621G>A) pathogenic?

MMAB p.Ala207= (c.621G>A) is classified Likely benign in MMAB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-15). Ultra-rare (popmax 0.0164%, mid); Associated with methylmalonic aciduria, cblB type.

What condition is associated with MMAB p.Ala207= (c.621G>A)?

MMAB p.Ala207= (c.621G>A) is associated with methylmalonic aciduria, cblB type (ClinVar).

How common is MMAB p.Ala207= (c.621G>A) in the general population?

MMAB p.Ala207= (c.621G>A) is ultra-rare (popmax 0.0164%, mid) (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.Ala207=

c.621G>A · rs769869903 · VCV1915497

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -2.5	GERP -3.9
Overall
CADD	4.289	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,613,780 alleles · ultra-rare exomes 5/1,461,602 · genomes 1/152,178 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
African / African-American	0.00133%	74,924
European (non-Finnish)	0.000339%	294,976

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.Ala207=
Coding: c.621G>A
MANE Select: NM_052845
dbSNP: rs769869903
Type: single nucleotide variant
Location: chr12:109559119 (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 207: an α-helix

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.Ala207Glu Uncertain significance ★ ⚠ same residue
MMAB p.Ala207Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala207 (accessed [today's date]).

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