Is PHKA1 p.Val375fs (c.1123_1124del) pathogenic?

PHKA1 p.Val375fs (c.11231124del) is classified Pathogenic in PHKA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). Associated with glycogen storage disease IXd.

What condition is associated with PHKA1 p.Val375fs (c.1123_1124del)?

PHKA1 p.Val375fs (c.1123_1124del) is associated with glycogen storage disease IXd (ClinVar).

PHKA1 p.Val375fs

Q: How is Glycogen storage disease due to muscle phosphorylase kinase deficiency inherited?

Typically Autosomal recessive, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1123_1124del · VCV3726560

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

glycogen storage disease IXd

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 11 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -3.5, phastCons 0.77

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

Variant & gene context

Gene: PHKA1
Protein: p.Val375fs
Coding: c.1123_1124del
MANE Select: NM_002637
Type: Microsatellite
Location: chrX:72653448 (GRCh38)
Structure: AlphaFold pLDDT 81.84 · 10 PDB

Full PHKA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Glycogen storage disease due to muscle phosphorylase kinase deficiency (Orphanet):

Inheritance: Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult

Similar variants

PHKA1 p.Ser868fs Pathogenic ★★ same condition
PHKA1 c.78+16TC[2] Likely benign ★★ same condition
PHKA1 p.Asp272fs Pathogenic ★ same condition
PHKA1 c.2685+8_2685+10del Conflicting classifications of pathogenicity ★ same condition
PHKA1 p.Ser1094fs Uncertain significance ★ same condition
PHKA1 p.Thr696del Uncertain significance ★ same condition
PHKA1 c.1042-13_1042-10del Likely benign ★ same condition
PHKA1 c.3244-29_3244-15del Likely benign ★ 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/phka1-p-val375fs (accessed [today's date]).

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