Is PHKA1 p.Ser244= (c.732A>C) pathogenic?

PHKA1 p.Ser244= (c.732A>C) is classified Likely benign in PHKA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-26). Very rare (popmax 8.27e-05%); Associated with glycogen storage disease IXd.

What condition is associated with PHKA1 p.Ser244= (c.732A>C)?

PHKA1 p.Ser244= (c.732A>C) is associated with glycogen storage disease IXd (ClinVar).

How common is PHKA1 p.Ser244= (c.732A>C) in the general population?

PHKA1 p.Ser244= (c.732A>C) is very rare (popmax 8.27e-05%) (gnomAD).

PHKA1 p.Ser244=

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.732A>C · rs1556306385 · VCV2189461

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.27e-05%)

Conditions

glycogen storage disease IXd

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -2.7
Overall
CADD	1.472	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.27e-05%

Overall 8.27e-05% 1/1,209,260 alleles · very rare exomes 1/1,095,655 · genomes 0/113,605 · 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: PHKA1
Protein: p.Ser244=
Coding: c.732A>C
MANE Select: NM_002637
dbSNP: rs1556306385
Type: single nucleotide variant
Location: chrX:72666283 (GRCh38)
Structure: AlphaFold pLDDT 81.84 · 10 PDB
Residue 244: an α-helix

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.Ser244Ala Uncertain significance ★ ⚠ same residue
PHKA1 c.2137+1G>A Likely pathogenic ★★ same condition
PHKA1 c.2527-1G>T Likely pathogenic ★★ same condition
PHKA1 c.2606+1G>A Pathogenic/Likely pathogenic ★★ same condition
PHKA1 c.537+1G>A Likely pathogenic ★★ same condition
PHKA1 p.Arg298Ter Pathogenic ★★ same condition
PHKA1 p.Arg392Ter Pathogenic/Likely pathogenic ★★ same condition
PHKA1 p.Arg739Ter 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/phka1-p-ser244 (accessed [today's date]).

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