Is PHKA1 p.Phe164= (c.492C>T) pathogenic?

PHKA1 p.Phe164= (c.492C>T) is classified Benign/Likely benign in PHKA1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.43%, afr); Associated with glycogen storage disease IXd.

What condition is associated with PHKA1 p.Phe164= (c.492C>T)?

PHKA1 p.Phe164= (c.492C>T) is associated with glycogen storage disease IXd (ClinVar).

How common is PHKA1 p.Phe164= (c.492C>T) in the general population?

PHKA1 p.Phe164= (c.492C>T) is low-frequency (popmax 1.43%, afr) (gnomAD).

PHKA1 p.Phe164=

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.492C>T · rs149354112 · VCV368652

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.43%, afr)

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 6.5	GERP -0.017, phastCons 1
Overall
CADD	10.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.43% African / African-American · 811/56,730 alleles

Filtering AF 1.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.32%

Overall 0.0758% 896/1,182,800 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.43%	70
Remaining individualsnot grpmax-eligible	0.0943%	1,060
Admixed American	0.0634%	1,577
Middle Eastern	0.0474%	2,110
South Asian	0.00535%	18,690
European (non-Finnish)	0.000804%	124,380

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.Phe164=
Coding: c.492C>T
MANE Select: NM_002637
dbSNP: rs149354112
Type: single nucleotide variant
Location: chrX:72684543 (GRCh38)
Structure: AlphaFold pLDDT 81.84 · 10 PDB
Residue 164: 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 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
PHKA1 p.Arg863Ter 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-phe164 (accessed [today's date]).

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