Is PHKA1 p.Asp127= (c.381T>C) pathogenic?

PHKA1 p.Asp127= (c.381T>C) is classified Benign in PHKA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-14). Rare (popmax 0.141%, sas); Associated with glycogen storage disease IXd.

What condition is associated with PHKA1 p.Asp127= (c.381T>C)?

PHKA1 p.Asp127= (c.381T>C) is associated with glycogen storage disease IXd (ClinVar).

How common is PHKA1 p.Asp127= (c.381T>C) in the general population?

PHKA1 p.Asp127= (c.381T>C) is rare (popmax 0.141%, sas) (gnomAD).

PHKA1 p.Asp127=

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.381T>C · rs781912629 · VCV2414106

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.141%, sas)

Conditions

glycogen storage disease IXd

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.9, phastCons 0.99
Overall
CADD	7.823	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.141% South Asian · 80/56,576 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.00698% 84/1,203,320 alleles · rare exomes 79/1,092,328 · genomes 5/110,992 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.141%	707
Remaining individualsnot grpmax-eligible	0.00633%	15,795
African / African-American	0.00176%	56,787

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.Asp127=
Coding: c.381T>C
MANE Select: NM_002637
dbSNP: rs781912629
Type: single nucleotide variant
Location: chrX:72695781 (GRCh38)
Structure: AlphaFold pLDDT 81.84 · 10 PDB
Residue 127: 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-asp127 (accessed [today's date]).

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