Is MMAA p.Ser402= (c.1206C>T) pathogenic?

MMAA p.Ser402= (c.1206C>T) is classified Likely benign in MMAA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-25). Absent from gnomAD v4.1; Associated with methylmalonic aciduria, cblA type.

What condition is associated with MMAA p.Ser402= (c.1206C>T)?

MMAA p.Ser402= (c.1206C>T) is associated with methylmalonic aciduria, cblA type (ClinVar).

How common is MMAA p.Ser402= (c.1206C>T) in the general population?

MMAA p.Ser402= (c.1206C>T) 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.

MMAA p.Ser402=

c.1206C>T · rs1374931888 · VCV1137472

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.43	GERP -3.3, phastCons 0.99
Overall
CADD	7.764	PHRED · no single calibrated threshold — expert panels disagree

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: MMAA
Protein: p.Ser402=
Coding: c.1206C>T
MANE Select: NM_172250
dbSNP: rs1374931888
Type: single nucleotide variant
Location: chr4:145655383 (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 402: 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 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
MMAA c.820-2A>G Likely pathogenic ★★ same condition
MMAA p.Arg145Gln 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-ser402 (accessed [today's date]).

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