Is PHKA1 p.Ala875= (c.2625G>A) pathogenic?

PHKA1 p.Ala875= (c.2625G>A) is classified Likely benign in PHKA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-14). Very rare (popmax 0.00219%, amr); Associated with glycogen storage disease IXd.

What condition is associated with PHKA1 p.Ala875= (c.2625G>A)?

PHKA1 p.Ala875= (c.2625G>A) is associated with glycogen storage disease IXd (ClinVar).

How common is PHKA1 p.Ala875= (c.2625G>A) in the general population?

PHKA1 p.Ala875= (c.2625G>A) is very rare (popmax 0.00219%, amr) (gnomAD).

PHKA1 p.Ala875=

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.2625G>A · rs781930090 · VCV1603481

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

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 -2.6
Overall
CADD	0.322	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00219% Admixed American · 1/45,744 alleles

Filtering AF 0.000477% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000346%

Overall 0.000999% 12/1,201,682 alleles · very rare exomes 11/1,089,399 · genomes 1/112,283 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00219%	45,744
South Asian	0.00177%	56,591
African / African-American	0.00175%	57,119
European (non-Finnish)	0.00101%	98,620

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.Ala875=
Coding: c.2625G>A
MANE Select: NM_002637
dbSNP: rs781930090
Type: single nucleotide variant
Location: chrX:72605601 (GRCh38)
Structure: AlphaFold pLDDT 81.84 · 10 PDB
Residue 875: 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.Ala875Thr 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-ala875 (accessed [today's date]).

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