Is PHKA2 p.Pro1205= (c.3615G>C) pathogenic?

PHKA2 p.Pro1205= (c.3615G>C) is classified Likely benign in PHKA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-18). Ultra-rare (popmax 0.0371%, amr); Associated with glycogen storage disease IXa1.

What condition is associated with PHKA2 p.Pro1205= (c.3615G>C)?

PHKA2 p.Pro1205= (c.3615G>C) is associated with glycogen storage disease IXa1 (ClinVar).

How common is PHKA2 p.Pro1205= (c.3615G>C) in the general population?

PHKA2 p.Pro1205= (c.3615G>C) is ultra-rare (popmax 0.0371%, amr) (gnomAD).

PHKA2 p.Pro1205=

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.3615G>C · rs200550207 · VCV2860103

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0371%, amr)

Conditions

glycogen storage disease IXa1

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -7.2	GERP -3.5
Overall
CADD	0.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0371% Admixed American · 17/45,867 alleles

Filtering AF 0.0236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0193%

Overall 0.00198% 24/1,210,006 alleles · ultra-rare exomes 14/1,097,449 · genomes 10/112,557 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0371%	2,698
Remaining individualsnot grpmax-eligible	0.0126%	7,934
African / African-American	0.00174%	57,436

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.Pro1205=
Coding: c.3615G>C
MANE Select: NM_000292
dbSNP: rs200550207
Type: single nucleotide variant
Location: chrX:18893578 (GRCh38)

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)

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-pro1205 (accessed [today's date]).

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