Is PHKA2 p.Val1127fs (c.3371_3377dup) pathogenic?

PHKA2 p.Val1127fs (c.33713377dup) is classified Pathogenic in PHKA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-14). Absent from gnomAD; Associated with glycogen storage disease IXa1.

What condition is associated with PHKA2 p.Val1127fs (c.3371_3377dup)?

PHKA2 p.Val1127fs (c.3371_3377dup) is associated with glycogen storage disease IXa1 (ClinVar).

How common is PHKA2 p.Val1127fs (c.3371_3377dup) in the general population?

PHKA2 p.Val1127fs (c.3371_3377dup) is absent from gnomAD (gnomAD).

PHKA2 p.Val1127fs

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.3371_3377dup · rs2047492720 · VCV858405

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

glycogen storage disease IXa1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 32 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.6	GERP -3.5

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHKA2
Protein: p.Val1127fs
Coding: c.3371_3377dup
MANE Select: NM_000292
dbSNP: rs2047492720
Type: Duplication
Location: chrX:18894363 (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

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 c.3336+1dup Likely pathogenic ★ same condition
PHKA2 p.His694fs Likely pathogenic ★ same condition
PHKA2 p.Leu1215_Thr1216insIle Likely pathogenic ★ same condition
PHKA2 p.Met1010fs Pathogenic ★ same condition
PHKA2 c.2597+2dup Conflicting classifications of pathogenicity ★ same condition
PHKA2 p.Asp757Ter Pathogenic same condition
PHKA2 p.Gly812fs Likely pathogenic same condition
PHKA2 c.1325-2A>G 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-val1127fs (accessed [today's date]).

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