Is ALDOA p.Ile245Val (c.733A>G) pathogenic?

ALDOA p.Ile245Val (c.733A>G) is classified Uncertain significance in ALDOA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-08). AlphaMissense: likely benign (0.1379); Ultra-rare (popmax 0.02%, amr); Associated with glycogen storage disease due to aldolase A deficiency.

What condition is associated with ALDOA p.Ile245Val (c.733A>G)?

ALDOA p.Ile245Val (c.733A>G) is associated with glycogen storage disease due to aldolase A deficiency (ClinVar).

How common is ALDOA p.Ile245Val (c.733A>G) in the general population?

ALDOA p.Ile245Val (c.733A>G) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about ALDOA p.Ile245Val (c.733A>G)?

AlphaMissense predicts likely benign (score 0.1379) — an in-silico prediction, not a clinical call.

ALDOA p.Ile245Val

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.733A>G · rs1239332534 · VCV1964812

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1379 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease due to aldolase A deficiency

Computational evidence

Protein change
AlphaMissense	0.1379	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -9.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,311 bp · p 0.028 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 I191V vs ClinVar I245V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/59,998 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.000744% 12/1,613,938 alleles · ultra-rare

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.Ile245Val
Coding: c.733A>G
dbSNP: rs1239332534
Type: single nucleotide variant
Location: chr16:30069336 (GRCh38)

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

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-ile245val (accessed [today's date]).

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