Is PHKB p.Ile192Val (c.574A>G) pathogenic?

PHKB p.Ile192Val (c.574A>G) is classified Conflicting classifications of pathogenicity in PHKB (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1301); Rare (popmax 0.559%, mid); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Ile192Val (c.574A>G)?

PHKB p.Ile192Val (c.574A>G) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Ile192Val (c.574A>G) in the general population?

PHKB p.Ile192Val (c.574A>G) is rare (popmax 0.559%, mid) (gnomAD).

What do computational predictors say about PHKB p.Ile192Val (c.574A>G)?

AlphaMissense predicts likely benign (score 0.1301) — an in-silico prediction, not a clinical call.

PHKB p.Ile192Val

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

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

c.574A>G · rs117218785 · VCV516456

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1301 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.559%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
AlphaMissense	0.1301	likely benign
REVEL	0.625	indeterminate
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.559% Middle Eastern · 32/5,720 alleles

Filtering AF 0.407% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.355%

Overall 0.145% 2,082/1,437,504 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.559%	179
Ashkenazi Jewishnot grpmax-eligible	0.344%	291
European (non-Finnish)	0.165%	605
Finnishnot grpmax-eligible	0.151%	661
Remaining individualsnot grpmax-eligible	0.124%	809
Admixed American	0.0903%	1,107
South Asian	0.0354%	2,823
African / African-American	0.0237%	4,219

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: PHKB
Protein: p.Ile192Val
Coding: c.574A>G
MANE Select: NM_000293
dbSNP: rs117218785
Type: single nucleotide variant
Location: chr16:47515581 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.06 · 6 PDB

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

Disease context

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

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

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

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PHKB c.2896-1G>T Pathogenic ★★ same condition
PHKB c.306-2A>G Pathogenic/Likely pathogenic ★★ same condition
PHKB p.Arg103Ter Pathogenic/Likely pathogenic ★★ same condition
PHKB p.Arg429Ter 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/phkb-p-ile192val (accessed [today's date]).

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