Is PHKA2 p.Ser796fs (c.2387_2388del) pathogenic?

PHKA2 p.Ser796fs (c.23872388del) is classified Pathogenic/Likely pathogenic in PHKA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-20). Very rare (popmax 0.000112%, nfe); Associated with glycogen storage disease IXa1.

What condition is associated with PHKA2 p.Ser796fs (c.2387_2388del)?

PHKA2 p.Ser796fs (c.2387_2388del) is associated with glycogen storage disease IXa1 (ClinVar).

How common is PHKA2 p.Ser796fs (c.2387_2388del) in the general population?

PHKA2 p.Ser796fs (c.2387_2388del) is very rare (popmax 0.000112%, nfe) (gnomAD).

PHKA2 p.Ser796fs

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.2387_2388del · VCV4871739

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

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 22 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,168 alleles

Overall 8.25e-05% 1/1,211,478 alleles · very rare exomes 1/1,097,832 · genomes 0/113,646 · joint denominator

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.Ser796fs
Coding: c.2387_2388del
MANE Select: NM_000292
Type: Microsatellite
Location: chrX:18908029 (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 p.Ser796Pro Uncertain significance ★★ ⚠ same residue
PHKA2 c.1794-8_1794-6del Uncertain significance ★★ same condition
PHKA2 p.Thr793fs Pathogenic ★ same condition
PHKA2 p.Ser1221del Uncertain significance ★ same condition
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

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-ser796fs (accessed [today's date]).

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