Is PHKA2 p.Ile283= (c.849T>A) pathogenic?

PHKA2 p.Ile283= (c.849T>A) is classified Benign in PHKA2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Low-frequency (popmax 4.31%, afr); Associated with glycogen storage disease IXa1.

What condition is associated with PHKA2 p.Ile283= (c.849T>A)?

PHKA2 p.Ile283= (c.849T>A) is associated with glycogen storage disease IXa1 (ClinVar).

How common is PHKA2 p.Ile283= (c.849T>A) in the general population?

PHKA2 p.Ile283= (c.849T>A) is low-frequency (popmax 4.31%, afr) (gnomAD).

PHKA2 p.Ile283=

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.849T>A · rs61733284 · VCV255779

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.31%, afr)

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 1	GERP -1.9, phastCons 0.99
Overall
CADD	7.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.31% African / African-American · 2,470/57,331 alleles

Filtering AF 4.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.11%

Overall 0.293% 3,537/1,208,421 alleles · low-frequency exomes 2,073/1,095,930 · genomes 1,464/112,491 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.31%	23
Middle Eastern	1.03%	97
Ashkenazi Jewishnot grpmax-eligible	0.54%	185
Remaining individualsnot grpmax-eligible	0.488%	205
Admixed American	0.467%	214
European (non-Finnish)	0.0505%	1,981
South Asian	0.0106%	9,470

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.Ile283=
Coding: c.849T>A
MANE Select: NM_000292
dbSNP: rs61733284
Type: single nucleotide variant
Location: chrX:18941544 (GRCh38)
Structure: AlphaFold pLDDT 81.36

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 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
PHKA2 p.Arg295Cys Pathogenic/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-ile283 (accessed [today's date]).

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