Is PFKM p.Phe49= (c.147C>T) pathogenic?

PFKM p.Phe49= (c.147C>T) is classified Likely benign in PFKM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-22). Very rare (popmax 0.000594%, nfe); Associated with glycogen storage disease VII.

What condition is associated with PFKM p.Phe49= (c.147C>T)?

PFKM p.Phe49= (c.147C>T) is associated with glycogen storage disease VII (ClinVar).

How common is PFKM p.Phe49= (c.147C>T) in the general population?

PFKM p.Phe49= (c.147C>T) is very rare (popmax 0.000594%, nfe) (gnomAD).

PFKM p.Phe49=

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.147C>T · rs1301983188 · VCV1905200

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000594%, nfe)

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 4.1	GERP 1.9, phastCons 1
Overall
CADD	13.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000594% European (non-Finnish) · 7/1,178,464 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,460,186 alleles · very rare

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.Phe49=
Coding: c.147C>T
MANE Select: NM_000289
dbSNP: rs1301983188
Type: single nucleotide variant
Location: chr12:48130424 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.66 · 1 PDB
Residue 49: 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 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
PFKM c.1500+1G>A 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-phe49 (accessed [today's date]).

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