Is MMAA p.Phe12= (c.36C>T) pathogenic?

MMAA p.Phe12= (c.36C>T) is classified Likely benign in MMAA (ClinVar, Single submitter, 2 submitters; last evaluated 2019-06-05). Very rare (popmax 8.47e-05%, nfe); Associated with methylmalonic aciduria, cblA type.

What condition is associated with MMAA p.Phe12= (c.36C>T)?

MMAA p.Phe12= (c.36C>T) is associated with methylmalonic aciduria, cblA type (ClinVar).

How common is MMAA p.Phe12= (c.36C>T) in the general population?

MMAA p.Phe12= (c.36C>T) 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.Phe12=

c.36C>T · rs1661385949 · VCV1158925

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

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 -0.066	GERP 0.74, phastCons 0.48
Overall
CADD	7.112	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.2e-05% 1/1,614,184 alleles · very rare exomes 1/1,461,870 · genomes 0/152,314 · joint denominator

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.Phe12=
Coding: c.36C>T
MANE Select: NM_172250
dbSNP: rs1661385949
Type: single nucleotide variant
Location: chr4:145639175 (GRCh38)
Gene constraint: LOEUF 1.156 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.71 · 2 PDB

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-phe12 (accessed [today's date]).

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