Is PFKM p.Pro332= (c.996A>G) pathogenic?

PFKM p.Pro332= (c.996A>G) is classified Likely benign in PFKM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-12). Very rare (popmax 0.00833%, amr); Associated with glycogen storage disease VII.

What condition is associated with PFKM p.Pro332= (c.996A>G)?

PFKM p.Pro332= (c.996A>G) is associated with glycogen storage disease VII (ClinVar).

How common is PFKM p.Pro332= (c.996A>G) in the general population?

PFKM p.Pro332= (c.996A>G) is very rare (popmax 0.00833%, amr) (gnomAD).

PFKM p.Pro332=

Q: How is Glycogen storage disease due to muscle phosphofructokinase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.996A>G · rs778817129 · VCV2166476

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

glycogen storage disease VII

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 -0.35	GERP -4
Overall
CADD	7.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,014 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000372% 6/1,614,036 alleles · very rare exomes 4/1,461,844 · genomes 2/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,003
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: PFKM
Protein: p.Pro332=
Coding: c.996A>G
MANE Select: NM_000289
dbSNP: rs778817129
Type: single nucleotide variant
Location: chr12:48137780 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.66 · 1 PDB
Residue 332: the 'n-terminal catalytic pfk domain 1' region

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

Disease context

glycogen storage disease VII — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to muscle phosphofructokinase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

PFKM p.Pro332Leu Uncertain significance ★★ ⚠ same residue
PFKM c.1062+1G>A Likely pathogenic ★★ same condition
PFKM c.1128-2A>G Likely pathogenic ★★ same condition
PFKM c.1191+1G>A Likely pathogenic ★★ same condition
PFKM c.1412+1G>T Likely pathogenic ★★ same condition
PFKM c.1412+2T>C Likely pathogenic ★★ same condition
PFKM c.1413-2A>G Pathogenic/Likely pathogenic ★★ same condition
PFKM c.1413-64A>G 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/pfkm-p-pro332 (accessed [today's date]).

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