Is ALDOA p.Arg123= (c.369C>T) pathogenic?

ALDOA p.Arg123= (c.369C>T) is classified Likely benign in ALDOA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). Ultra-rare (popmax 0.033%, mid); Associated with glycogen storage disease due to aldolase A deficiency.

What condition is associated with ALDOA p.Arg123= (c.369C>T)?

ALDOA p.Arg123= (c.369C>T) is associated with glycogen storage disease due to aldolase A deficiency (ClinVar).

How common is ALDOA p.Arg123= (c.369C>T) in the general population?

ALDOA p.Arg123= (c.369C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

ALDOA p.Arg123=

Q: How is Glycogen storage disease due to aldolase A deficiency inherited?

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

c.369C>T · VCV4745193

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

glycogen storage disease due to aldolase A deficiency

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 -20	GERP -3.9
Overall
CADD	0.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00322% 52/1,613,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0274%	3,643
Remaining individualsnot grpmax-eligible	0.0128%	7,814
African / African-American	0.004%	25,007
European (non-Finnish)	0.00119%	84,288

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: ALDOA
Protein: p.Arg123=
Coding: c.369C>T
MANE Select: NM_001243177
Type: single nucleotide variant
Location: chr16:30067544 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.53 · 8 PDB
Residue 123: a β-strand

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

Disease context

glycogen storage disease due to aldolase A deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to aldolase A deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

ALDOA p.Arg123His Uncertain significance ★ same residue
ALDOA p.Arg123Cys Uncertain significance ★ ⚠ same residue
ALDOA p.Ala334Val Pathogenic/Likely pathogenic ★★ same condition
ALDOA c.274+5G>A Uncertain significance ★★ same condition
ALDOA p.Ala142Val Uncertain significance ★★ same condition
ALDOA p.Ala217Thr Uncertain significance ★★ same condition
ALDOA p.Ala310Val Uncertain significance ★★ same condition
ALDOA p.Ala377Ser Uncertain significance ★★ 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/aldoa-p-arg123 (accessed [today's date]).

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