Is PHKA2 p.Ile693Val (c.2077A>G) pathogenic?

PHKA2 p.Ile693Val (c.2077A>G) is classified Benign/Likely benign in PHKA2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0608); Low-frequency (popmax 2.65%, mid); Associated with glycogen storage disease IXa1.

What condition is associated with PHKA2 p.Ile693Val (c.2077A>G)?

PHKA2 p.Ile693Val (c.2077A>G) is associated with glycogen storage disease IXa1 (ClinVar).

How common is PHKA2 p.Ile693Val (c.2077A>G) in the general population?

PHKA2 p.Ile693Val (c.2077A>G) is low-frequency (popmax 2.65%, mid) (gnomAD).

What do computational predictors say about PHKA2 p.Ile693Val (c.2077A>G)?

AlphaMissense predicts likely benign (score 0.0608) — an in-silico prediction, not a clinical call.

PHKA2 p.Ile693Val

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.2077A>G · rs143732206 · VCV255771

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0608 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.65%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease IXa1

Computational evidence

Protein change
AlphaMissense	0.0608	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -3.2
Regional constraint	o/e 0.90	unconstrained · MANE · 45 kb · p 0.0065 · regional, not allelic
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.65% Middle Eastern · 115/4,347 alleles

Filtering AF 2.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.11%

Overall 0.973% 11,754/1,208,559 alleles · low-frequency exomes 10,995/1,096,245 · genomes 759/112,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.65%	38
South Asian	1.64%	61
Amishnot grpmax-eligible	1.61%	62
European (non-Finnish)	1.11%	90
Remaining individualsnot grpmax-eligible	0.841%	119
Ashkenazi Jewishnot grpmax-eligible	0.568%	176
Admixed American	0.269%	372
Finnishnot grpmax-eligible	0.169%	591
African / African-American	0.147%	682
East Asian	0.00592%	16,887

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.Ile693Val
Coding: c.2077A>G
MANE Select: NM_000292
dbSNP: rs143732206
Type: single nucleotide variant
Location: chrX:18918741 (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-ile693val (accessed [today's date]).

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