Is MMAA p.Ser183= (c.549T>C) pathogenic?

MMAA p.Ser183= (c.549T>C) is classified Likely benign in MMAA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-06). Very rare (popmax 8.47e-05%, nfe); Associated with methylmalonic aciduria, cblA type.

What condition is associated with MMAA p.Ser183= (c.549T>C)?

MMAA p.Ser183= (c.549T>C) is associated with methylmalonic aciduria, cblA type (ClinVar).

How common is MMAA p.Ser183= (c.549T>C) in the general population?

MMAA p.Ser183= (c.549T>C) is very rare (popmax 8.47e-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.

MMAA p.Ser183=

c.549T>C · rs2546337548 · VCV2874898

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

methylmalonic aciduria, cblA 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 -2.7
Overall
CADD	3.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,012 alleles

Overall 0.000137% 2/1,461,824 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,038
European (non-Finnish)grpmax	8.47e-05%	1,180,012

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MMAA
Protein: p.Ser183=
Coding: c.549T>C
MANE Select: NM_172250
dbSNP: rs2546337548
Type: single nucleotide variant
Location: chr4:145642472 (GRCh38)
Gene constraint: LOEUF 1.156 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.71 · 2 PDB
Residue 183: a UniProt-annotated variant site (in maca)

Full MMAA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

methylmalonic aciduria, cblA 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

MMAA p.Ser183fs Likely pathogenic ★ same residue
MMAA p.Ser183del Uncertain significance ★ same residue
MMAA c.440-2A>G Likely pathogenic ★★ same condition
MMAA c.562+2T>C Likely pathogenic ★★ same condition
MMAA c.733+1G>A Pathogenic/Likely pathogenic ★★ same condition
MMAA c.733+1G>T Pathogenic/Likely pathogenic ★★ same condition
MMAA c.820-1G>A Pathogenic/Likely pathogenic ★★ same condition
MMAA c.820-1G>C 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/mmaa-p-ser183 (accessed [today's date]).

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