Is MMAA p.Pro265= (c.795A>C) pathogenic?

MMAA p.Pro265= (c.795A>C) is classified Likely benign in MMAA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-10). Very rare (popmax 0.005%, amr); Associated with methylmalonic aciduria, cblA type.

What condition is associated with MMAA p.Pro265= (c.795A>C)?

MMAA p.Pro265= (c.795A>C) is associated with methylmalonic aciduria, cblA type (ClinVar).

How common is MMAA p.Pro265= (c.795A>C) in the general population?

MMAA p.Pro265= (c.795A>C) is very rare (popmax 0.005%, amr) (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.Pro265=

c.795A>C · rs767934772 · VCV795326

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 -1.5
Overall
CADD	9.373	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,030 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,614,146 alleles · very rare exomes 4/1,461,818 · genomes 0/152,328 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,010
European (non-Finnish)	8.47e-05%	1,179,984

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.Pro265=
Coding: c.795A>C
MANE Select: NM_172250
dbSNP: rs767934772
Type: single nucleotide variant
Location: chr4:145651123 (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 265: 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-pro265 (accessed [today's date]).

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