Is PHKB p.Ala1072= (c.3216G>A) pathogenic?

PHKB p.Ala1072= (c.3216G>A) is classified Conflicting classifications of pathogenicity in PHKB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-30). Rare (popmax 0.109%, sas); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Ala1072= (c.3216G>A)?

PHKB p.Ala1072= (c.3216G>A) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Ala1072= (c.3216G>A) in the general population?

PHKB p.Ala1072= (c.3216G>A) is rare (popmax 0.109%, sas) (gnomAD).

PHKB p.Ala1072=

Q: How is Glycogen storage disease due to liver and muscle phosphorylase kinase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.3216G>A · rs137869198 · VCV319365

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.109%, sas)

Conditions

glycogen storage disease IXb

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 -5.6	GERP -4.7
Overall
CADD	4.541	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% South Asian · 99/91,080 alleles

Filtering AF 0.0913% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0849%

Overall 0.0439% 708/1,614,084 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.109%	920
European (non-Finnish)	0.0455%	2,197
Remaining individualsnot grpmax-eligible	0.0432%	2,315
African / African-American	0.0293%	3,411
Admixed American	0.0233%	4,287
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
East Asian	0.00669%	14,959
Finnishnot grpmax-eligible	0.00469%	21,345

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: PHKB
Protein: p.Ala1072=
Coding: c.3216G>A
MANE Select: NM_000293
dbSNP: rs137869198
Type: single nucleotide variant
Location: chr16:47699300 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.06 · 6 PDB
Residue 1072: an α-helix

Full PHKB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease IXb — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to liver and muscle phosphorylase kinase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

PHKB p.Ala1072Thr Uncertain significance ★★ ⚠ same residue
PHKB p.Ala1072Val Uncertain significance ★★ ⚠ same residue
PHKB c.1127-2A>G Pathogenic/Likely pathogenic ★★ same condition
PHKB c.1364-2A>G Pathogenic ★★ same condition
PHKB c.1972-2A>G Pathogenic/Likely pathogenic ★★ same condition
PHKB c.2427+965A>C Pathogenic/Likely pathogenic ★★ same condition
PHKB c.2896-1G>T Pathogenic ★★ same condition
PHKB c.306-2A>G 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/phkb-p-ala1072 (accessed [today's date]).

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