Is PHKA1 p.Ser701Phe (c.2102C>T) pathogenic?

PHKA1 p.Ser701Phe (c.2102C>T) is classified Uncertain significance in PHKA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.2479); Very rare (popmax 0.00176%, sas); Associated with glycogen storage disease IXd.

What condition is associated with PHKA1 p.Ser701Phe (c.2102C>T)?

PHKA1 p.Ser701Phe (c.2102C>T) is associated with glycogen storage disease IXd (ClinVar).

How common is PHKA1 p.Ser701Phe (c.2102C>T) in the general population?

PHKA1 p.Ser701Phe (c.2102C>T) is very rare (popmax 0.00176%, sas) (gnomAD).

What do computational predictors say about PHKA1 p.Ser701Phe (c.2102C>T)?

AlphaMissense predicts likely benign (score 0.2479) — an in-silico prediction, not a clinical call.

PHKA1 p.Ser701Phe

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.2102C>T · rs868926138 · VCV2671674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2479 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00176%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease IXd

Computational evidence

Protein change
AlphaMissense	0.2479	likely benign
REVEL	0.846	moderately pathogenic-leaning
SaProt	LLR -8.10	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 54 kb · p 0.45 · regional, not allelic
Overall
CADD	25.1	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 0.00176% South Asian · 1/56,883 alleles

Overall 8.26e-05% 1/1,210,162 alleles · very rare exomes 1/1,097,162 · genomes 0/113,000 · 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.Ser701Phe
Coding: c.2102C>T
MANE Select: NM_002637
dbSNP: rs868926138
Type: single nucleotide variant
Location: chrX:72620760 (GRCh38)
Structure: AlphaFold pLDDT 81.84 · 10 PDB

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.Ser701_Leu702del 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-ser701phe (accessed [today's date]).

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