Is PHKA1 p.Asp512= (c.1536C>T) pathogenic?

PHKA1 p.Asp512= (c.1536C>T) is classified Likely benign in PHKA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-07). Very rare (popmax 0.000226%, nfe); Associated with glycogen storage disease IXd.

What condition is associated with PHKA1 p.Asp512= (c.1536C>T)?

PHKA1 p.Asp512= (c.1536C>T) is associated with glycogen storage disease IXd (ClinVar).

How common is PHKA1 p.Asp512= (c.1536C>T) in the general population?

PHKA1 p.Asp512= (c.1536C>T) is very rare (popmax 0.000226%, nfe) (gnomAD).

PHKA1 p.Asp512=

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.1536C>T · rs782285118 · VCV2867014

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000226%, nfe)

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 1.3	GERP 0.007, phastCons 1
Overall
CADD	6.746	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000226% European (non-Finnish) · 2/886,509 alleles

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

Overall 0.000333% 4/1,200,472 alleles · very rare exomes 3/1,088,629 · genomes 1/111,843 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00911%	10,971
European (non-Finnish)grpmax	0.000226%	443,255

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp512=
Coding: c.1536C>T
MANE Select: NM_002637
dbSNP: rs782285118
Type: single nucleotide variant
Location: chrX:72636310 (GRCh38)
Structure: AlphaFold pLDDT 81.84 · 10 PDB
Residue 512: a β-strand

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-asp512 (accessed [today's date]).

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