Is PHKA2 p.Arg1111Ter (c.3331C>T) pathogenic?

PHKA2 p.Arg1111Ter (c.3331C>T) is classified Pathogenic in PHKA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-03). Absent from gnomAD v4.1; Associated with glycogen storage disease IXa1.

What condition is associated with PHKA2 p.Arg1111Ter (c.3331C>T)?

PHKA2 p.Arg1111Ter (c.3331C>T) is associated with glycogen storage disease IXa1 (ClinVar).

How common is PHKA2 p.Arg1111Ter (c.3331C>T) in the general population?

PHKA2 p.Arg1111Ter (c.3331C>T) is absent from gnomAD v4.1 (gnomAD).

PHKA2 p.Arg1111Ter

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.3331C>T · rs1601689006 · VCV655569

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

glycogen storage disease IXa1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 31 of 33
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.3	GERP 0.85, phastCons 0.98
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PHKA2
Protein: p.Arg1111Ter
Coding: c.3331C>T
MANE Select: NM_000292
dbSNP: rs1601689006
Type: single nucleotide variant
Location: chrX:18895143 (GRCh38)
Structure: AlphaFold pLDDT 81.36
Residue 1111: a UniProt-annotated variant site (in gsd9a; type 2)

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.Arg1111Gln 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.Arg186Cys Pathogenic/Likely pathogenic ★★ same condition
PHKA2 p.Arg186His Likely pathogenic ★★ same condition
PHKA2 p.Arg295Cys 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-arg1111ter (accessed [today's date]).

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