Is PHKA2 p.Ser1053= (c.3159G>A) pathogenic?

PHKA2 p.Ser1053= (c.3159G>A) is classified Likely benign in PHKA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-14). Very rare (popmax 0.00218%, amr); Associated with glycogen storage disease IXa1.

What condition is associated with PHKA2 p.Ser1053= (c.3159G>A)?

PHKA2 p.Ser1053= (c.3159G>A) is associated with glycogen storage disease IXa1 (ClinVar).

How common is PHKA2 p.Ser1053= (c.3159G>A) in the general population?

PHKA2 p.Ser1053= (c.3159G>A) is very rare (popmax 0.00218%, amr) (gnomAD).

PHKA2 p.Ser1053=

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.3159G>A · rs766231884 · VCV2065751

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00218%, amr)

Conditions

glycogen storage disease IXa1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -15	GERP -3.5
Overall
CADD	0.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00218% Admixed American · 1/45,794 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000331% 4/1,209,199 alleles · very rare exomes 3/1,097,434 · genomes 1/111,765 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00218%	45,794
African / African-American	0.00175%	57,141
European (non-Finnish)	0.000223%	447,493

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.Ser1053=
Coding: c.3159G>A
MANE Select: NM_000292
dbSNP: rs766231884
Type: single nucleotide variant
Location: chrX:18897286 (GRCh38)
Structure: AlphaFold pLDDT 81.36
Residue 1053: the 'disordered' region

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.Ser1053Leu Likely benign ★ same residue
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
PHKA2 p.Arg1111Ter Pathogenic ★★ same condition
PHKA2 p.Arg186Cys Pathogenic/Likely pathogenic ★★ same condition
PHKA2 p.Arg186His 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-ser1053 (accessed [today's date]).

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