Is PHKB p.Met883Val (c.2647A>G) pathogenic?

PHKB p.Met883Val (c.2647A>G) is classified Uncertain significance in PHKB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-28). AlphaMissense: likely benign (0.3335); Ultra-rare (popmax 0.0165%, mid); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Met883Val (c.2647A>G)?

PHKB p.Met883Val (c.2647A>G) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Met883Val (c.2647A>G) in the general population?

PHKB p.Met883Val (c.2647A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PHKB p.Met883Val (c.2647A>G)?

AlphaMissense predicts likely benign (score 0.3335) — an in-silico prediction, not a clinical call.

PHKB p.Met883Val

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.2647A>G · VCV3697301

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3335 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
AlphaMissense	0.3335	likely benign
REVEL	0.881	moderately pathogenic-leaning
SaProt	LLR -11.51	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	24.4	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 0.0165% Middle Eastern · 1/6,076 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000805% 13/1,613,950 alleles · ultra-rare exomes 12/1,461,806 · genomes 1/152,144 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,076
Admixed American	0.00167%	59,976
European (non-Finnish)	0.000932%	107,271

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.Met883Val
Coding: c.2647A>G
MANE Select: NM_000293
Type: single nucleotide variant
Location: chr16:47689057 (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 883: 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-met883val (accessed [today's date]).

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