Is MMAA p.Pro6fs (c.15_16del) pathogenic?

MMAA p.Pro6fs (c.1516del) is classified Likely pathogenic in MMAA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-03-06). No gnomAD frequency available for this variant; Associated with methylmalonic aciduria, cblA type.

What condition is associated with MMAA p.Pro6fs (c.15_16del)?

MMAA p.Pro6fs (c.15_16del) is associated with methylmalonic aciduria, cblA type (ClinVar).

How common is MMAA p.Pro6fs (c.15_16del) in the general population?

MMAA p.Pro6fs (c.15_16del) is no gnomAD frequency available for this variant (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.Pro6fs

c.15_16del · rs1553957862 · VCV552349

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

methylmalonic aciduria, cblA type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MMAA
Protein: p.Pro6fs
Coding: c.15_16del
MANE Select: NM_172250
dbSNP: rs1553957862
Type: Deletion
Location: chr4:145639154 (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.439+4_439+7del Likely pathogenic ★★ same condition
MMAA c.963_969+4del Pathogenic/Likely pathogenic ★★ same condition
MMAA p.Arg214fs Pathogenic/Likely pathogenic ★★ same condition
MMAA p.Asn137fs Pathogenic/Likely pathogenic ★★ same condition
MMAA p.Gln372fs Pathogenic/Likely pathogenic ★★ same condition
MMAA p.His130fs Pathogenic ★★ same condition
MMAA p.Phe345fs Pathogenic ★★ same condition
MMAA p.Pro152fs 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-pro6fs (accessed [today's date]).

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