Is PHKA1 p.Ser868fs (c.2603_2604del) pathogenic?

PHKA1 p.Ser868fs (c.26032604del) is classified Pathogenic in PHKA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-23). Very rare (popmax 0.000228%, nfe); Associated with glycogen storage disease IXd.

What condition is associated with PHKA1 p.Ser868fs (c.2603_2604del)?

PHKA1 p.Ser868fs (c.2603_2604del) is associated with glycogen storage disease IXd (ClinVar).

How common is PHKA1 p.Ser868fs (c.2603_2604del) in the general population?

PHKA1 p.Ser868fs (c.2603_2604del) is very rare (popmax 0.000228%, nfe) (gnomAD).

PHKA1 p.Ser868fs

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.2603_2604del · rs2052776972 · VCV1033522

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000228%, nfe)

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 23 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000228% European (non-Finnish) · 2/878,108 alleles

Filtering AF 3.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000185% 2/1,078,990 alleles · very rare

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: PHKA1
Protein: p.Ser868fs
Coding: c.2603_2604del
MANE Select: NM_002637
dbSNP: rs2052776972
Type: Microsatellite
Location: chrX:72609626 (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.Ser868Phe Uncertain significance ★ ⚠ same residue
PHKA1 c.78+16TC[2] Likely benign ★★ same condition
PHKA1 p.Asp272fs Pathogenic ★ same condition
PHKA1 p.Val375fs 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

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-ser868fs (accessed [today's date]).

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