Is PFKM p.Phe652= (c.1956C>T) pathogenic?

PFKM p.Phe652= (c.1956C>T) is classified Likely benign in PFKM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.016%, afr); Associated with glycogen storage disease VII.

What condition is associated with PFKM p.Phe652= (c.1956C>T)?

PFKM p.Phe652= (c.1956C>T) is associated with glycogen storage disease VII (ClinVar).

How common is PFKM p.Phe652= (c.1956C>T) in the general population?

PFKM p.Phe652= (c.1956C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

PFKM p.Phe652=

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.1956C>T · rs771733776 · VCV1096409

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

glycogen storage disease VII

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.63 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.4	GERP -4
Overall
CADD	8.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,920 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00217% 35/1,613,272 alleles · ultra-rare exomes 30/1,461,102 · genomes 5/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,243
Admixed American	0.005%	19,997
European (non-Finnish)	0.00161%	62,072
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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.Phe652=
Coding: c.1956C>T
MANE Select: NM_000289
dbSNP: rs771733776
Type: single nucleotide variant
Location: chr12:48144121 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.66 · 1 PDB
Residue 652: the 'c-terminal regulatory pfk domain 2' 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-phe652 (accessed [today's date]).

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