Is ALDOA p.Arg188Cys (c.562C>T) pathogenic?

ALDOA p.Arg188Cys (c.562C>T) is classified Uncertain significance in ALDOA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-25). AlphaMissense: likely pathogenic (0.9385); Very rare (popmax 0.00267%, afr); Associated with glycogen storage disease due to aldolase A deficiency.

What condition is associated with ALDOA p.Arg188Cys (c.562C>T)?

ALDOA p.Arg188Cys (c.562C>T) is associated with glycogen storage disease due to aldolase A deficiency (ClinVar).

How common is ALDOA p.Arg188Cys (c.562C>T) in the general population?

ALDOA p.Arg188Cys (c.562C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ALDOA p.Arg188Cys (c.562C>T)?

AlphaMissense predicts likely pathogenic (score 0.9385) — an in-silico prediction, not a clinical call.

ALDOA p.Arg188Cys

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.562C>T · rs11553113 · VCV2169337

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9385 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease due to aldolase A deficiency

Computational evidence

Protein change
AlphaMissense	0.9385	likely pathogenic
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -15.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,311 bp · p 0.028 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R134C vs ClinVar R188C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,918 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00118% 19/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,459
East Asian	0.00223%	44,896
European (non-Finnish)	0.00127%	78,670
South Asian	0.0011%	91,092

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.Arg188Cys
Coding: c.562C>T
MANE Select: NM_001243177
dbSNP: rs11553113
Type: single nucleotide variant
Location: chr16:30068838 (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 188: an active site; 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.Arg188His 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
ALDOA p.Ala74Thr 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-arg188cys (accessed [today's date]).

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