Is PHKB p.Val762Ile (c.2284G>A) pathogenic?

PHKB p.Val762Ile (c.2284G>A) is classified Conflicting classifications of pathogenicity in PHKB (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0767); Rare (popmax 0.243%, afr); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Val762Ile (c.2284G>A)?

PHKB p.Val762Ile (c.2284G>A) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Val762Ile (c.2284G>A) in the general population?

PHKB p.Val762Ile (c.2284G>A) is rare (popmax 0.243%, afr) (gnomAD).

What do computational predictors say about PHKB p.Val762Ile (c.2284G>A)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

PHKB p.Val762Ile

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.2284G>A · rs56010117 · VCV785532

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.243%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -9.42	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 2.1	GERP -0.9, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	16.85	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 0.243% African / African-American · 182/74,968 alleles

Filtering AF 0.214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.203%

Overall 0.0192% 309/1,612,344 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.243%	412
Remaining individualsnot grpmax-eligible	0.0625%	1,601
East Asian	0.0424%	2,360
Admixed American	0.035%	2,856
Middle Eastern	0.0165%	6,048
South Asian	0.0143%	7,002
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,794
European (non-Finnish)	0.00272%	36,830

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.Val762Ile
Coding: c.2284G>A
MANE Select: NM_000293
dbSNP: rs56010117
Type: single nucleotide variant
Location: chr16:47663682 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.06 · 6 PDB
Residue 762: an α-helix

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.2427+965A>C Pathogenic/Likely pathogenic ★★ same condition
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-val762ile (accessed [today's date]).

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