Is PHKG2 p.Phe172= (c.516C>T) pathogenic?

PHKG2 p.Phe172= (c.516C>T) is classified Likely benign in PHKG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). Ultra-rare (popmax 0.0658%, mid); Associated with glycogen storage disease IXc.

What condition is associated with PHKG2 p.Phe172= (c.516C>T)?

PHKG2 p.Phe172= (c.516C>T) is associated with glycogen storage disease IXc (ClinVar).

How common is PHKG2 p.Phe172= (c.516C>T) in the general population?

PHKG2 p.Phe172= (c.516C>T) is ultra-rare (popmax 0.0658%, mid) (gnomAD).

PHKG2 p.Phe172=

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.516C>T · rs758301470 · VCV1590933

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0658%, mid)

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 0.63	GERP -2.6, phastCons 1
Overall
CADD	13.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0658% Middle Eastern · 4/6,082 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00359% 58/1,613,990 alleles · ultra-rare exomes 49/1,461,876 · genomes 9/152,114 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0658%	1,521
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.00364%	27,442
African / African-American	0.00267%	37,453
South Asian	0.0022%	45,541
Admixed American	0.00167%	59,984

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.Phe172=
Coding: c.516C>T
MANE Select: NM_000294
dbSNP: rs758301470
Type: single nucleotide variant
Location: chr16:30753517 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.77 · 1 PDB
Residue 172: the protein kinase domain

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-phe172 (accessed [today's date]).

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