Is PHKA2 p.Arg1063= (c.3187C>A) pathogenic?

PHKA2 p.Arg1063= (c.3187C>A) is classified Benign/Likely benign in PHKA2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-19). Rare (popmax 0.323%, amr); Associated with glycogen storage disease IXa1.

What condition is associated with PHKA2 p.Arg1063= (c.3187C>A)?

PHKA2 p.Arg1063= (c.3187C>A) is associated with glycogen storage disease IXa1 (ClinVar).

How common is PHKA2 p.Arg1063= (c.3187C>A) in the general population?

PHKA2 p.Arg1063= (c.3187C>A) is rare (popmax 0.323%, amr) (gnomAD).

PHKA2 p.Arg1063=

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.3187C>A · rs139136352 · VCV384861

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.323%, amr)

Conditions

glycogen storage disease IXa1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Overall
CADD	11.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.323% Admixed American · 148/45,795 alleles

Filtering AF 0.281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.265%

Overall 0.039% 471/1,208,631 alleles · rare exomes 385/1,097,105 · genomes 86/111,526 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.6%	167
Admixed Americangrpmax	0.323%	309
Remaining individualsnot grpmax-eligible	0.111%	898
European (non-Finnish)	0.0146%	6,829
African / African-American	0.0122%	8,165

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1063=
Coding: c.3187C>A
MANE Select: NM_000292
dbSNP: rs139136352
Type: single nucleotide variant
Location: chrX:18897258 (GRCh38)
Structure: AlphaFold pLDDT 81.36
Residue 1063: the 'calmodulin-binding' region

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

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.Arg1063Trp Uncertain significance ★ ⚠ same residue
PHKA2 p.Arg1063Gln 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

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-arg1063 (accessed [today's date]).

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