Is PHKA2 p.Arg930Trp (c.2788C>T) pathogenic?

PHKA2 p.Arg930Trp (c.2788C>T) is classified Conflicting classifications of pathogenicity in PHKA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.154); Rare (popmax 0.112%, sas); Associated with glycogen storage disease IXa1.

What condition is associated with PHKA2 p.Arg930Trp (c.2788C>T)?

PHKA2 p.Arg930Trp (c.2788C>T) is associated with glycogen storage disease IXa1, intellectual disability (ClinVar).

How common is PHKA2 p.Arg930Trp (c.2788C>T) in the general population?

PHKA2 p.Arg930Trp (c.2788C>T) is rare (popmax 0.112%, sas) (gnomAD).

What do computational predictors say about PHKA2 p.Arg930Trp (c.2788C>T)?

AlphaMissense predicts likely benign (score 0.154) — an in-silico prediction, not a clinical call.

PHKA2 p.Arg930Trp

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.2788C>T · VCV3704613

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.154 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease IXa1

Computational evidence

Protein change
AlphaMissense	0.154	likely benign
REVEL	0.71	pathogenic-leaning
SaProt	LLR -12.40	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP -1.8, phastCons 0.89
Regional constraint	o/e 0.90	unconstrained · MANE · 45 kb · p 0.0065 · regional, not allelic
Overall
CADD	21.5	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 0.112% South Asian · 64/56,922 alleles

Filtering AF 0.0904% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0822%

Overall 0.00851% 103/1,210,926 alleles · rare exomes 96/1,097,806 · genomes 7/113,120 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.112%	889
Finnishnot grpmax-eligible	0.00641%	15,596
Remaining individualsnot grpmax-eligible	0.0042%	23,813
European (non-Finnish)	0.00369%	27,126
Admixed American	0.00217%	45,992

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: PHKA2
Protein: p.Arg930Trp
Coding: c.2788C>T
MANE Select: NM_000292
Type: single nucleotide variant
Location: chrX:18906513 (GRCh38)
Structure: AlphaFold pLDDT 81.36

Full PHKA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease IXa1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability

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

PHKA2 p.Arg930Gln Uncertain significance ★★ ⚠ same residue
PHKA2 c.1325-2A>G Likely pathogenic ★★ same condition
PHKA2 c.2597+1G>A Pathogenic/Likely pathogenic ★★ same condition
PHKA2 c.537+2T>C Pathogenic/Likely pathogenic ★★ same condition
PHKA2 c.918+1G>A Pathogenic/Likely pathogenic ★★ same condition
PHKA2 p.Arg1111Ter Pathogenic ★★ same condition
PHKA2 p.Arg186Cys Pathogenic/Likely pathogenic ★★ same condition
PHKA2 p.Arg186His 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/phka2-p-arg930trp (accessed [today's date]).

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