Is PHKA1 p.Val1087Phe (c.3259G>T) pathogenic?

PHKA1 p.Val1087Phe (c.3259G>T) is classified Uncertain significance in PHKA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-25). AlphaMissense: likely pathogenic (0.6227); Very rare (popmax 0.000112%, nfe); Associated with glycogen storage disease IXd.

What condition is associated with PHKA1 p.Val1087Phe (c.3259G>T)?

PHKA1 p.Val1087Phe (c.3259G>T) is associated with glycogen storage disease IXd (ClinVar).

How common is PHKA1 p.Val1087Phe (c.3259G>T) in the general population?

PHKA1 p.Val1087Phe (c.3259G>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about PHKA1 p.Val1087Phe (c.3259G>T)?

AlphaMissense predicts likely pathogenic (score 0.6227) — an in-silico prediction, not a clinical call.

PHKA1 p.Val1087Phe

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.3259G>T · VCV3630103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6227 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease IXd

Computational evidence

Protein change
AlphaMissense	0.6227	likely pathogenic
REVEL	0.812	moderately pathogenic-leaning
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 54 kb · p 0.45 · regional, not allelic
Overall
CADD	23.2	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 0.000112% European (non-Finnish) · 1/892,554 alleles

Overall 8.28e-05% 1/1,208,219 alleles · very rare exomes 1/1,094,822 · genomes 0/113,397 · joint denominator

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.Val1087Phe
Coding: c.3259G>T
MANE Select: NM_002637
Type: single nucleotide variant
Location: chrX:72584287 (GRCh38)
Structure: AlphaFold pLDDT 81.84 · 10 PDB
Residue 1087: 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-val1087phe (accessed [today's date]).

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