Is PHKG2 p.Pro7= (c.21G>C) pathogenic?

PHKG2 p.Pro7= (c.21G>C) is classified Likely benign in PHKG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). Ultra-rare (popmax 0.0618%, sas); Associated with glycogen storage disease IXc.

What condition is associated with PHKG2 p.Pro7= (c.21G>C)?

PHKG2 p.Pro7= (c.21G>C) is associated with glycogen storage disease IXc (ClinVar).

How common is PHKG2 p.Pro7= (c.21G>C) in the general population?

PHKG2 p.Pro7= (c.21G>C) is ultra-rare (popmax 0.0618%, sas) (gnomAD).

PHKG2 p.Pro7=

Q: How is Glycogen storage disease due to liver phosphorylase kinase deficiency inherited?

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

c.21G>C · rs200427925 · VCV2724503

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0618%, sas)

Conditions

glycogen storage disease IXc

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 -0.23	GERP -5.3, phastCons 0.006
Overall
CADD	10.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0618% South Asian · 52/84,166 alleles

Filtering AF 0.0483% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0436%

Overall 0.00425% 66/1,552,750 alleles · ultra-rare exomes 63/1,400,426 · genomes 3/152,324 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0618%	1,619
Middle Eastern	0.0167%	5,982
Remaining individualsnot grpmax-eligible	0.00665%	15,042
Admixed American	0.00196%	51,148
European (non-Finnish)	0.000697%	143,451

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: PHKG2
Protein: p.Pro7=
Coding: c.21G>C
MANE Select: NM_000294
dbSNP: rs200427925
Type: single nucleotide variant
Location: chr16:30748841 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.77 · 1 PDB

Full PHKG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Glycogen storage disease due to liver phosphorylase kinase deficiency (Orphanet):

Inheritance: Autosomal recessive, X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

PHKG2 c.96-11G>A Pathogenic/Likely pathogenic ★★ same condition
PHKG2 p.Arg152Ter Pathogenic/Likely pathogenic ★★ same condition
PHKG2 p.Arg185Ter Pathogenic ★★ same condition
PHKG2 p.Arg279Cys Pathogenic/Likely pathogenic ★★ same condition
PHKG2 p.Arg309Trp Likely pathogenic ★★ ⚠ same condition
PHKG2 p.Arg44Ter Pathogenic ★★ same condition
PHKG2 p.Arg76Ter Pathogenic/Likely pathogenic ★★ same condition
PHKG2 p.Asp215Asn 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/phkg2-p-pro7 (accessed [today's date]).

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