Is ALDOA p.Pro239Ser (c.715C>T) pathogenic?

ALDOA p.Pro239Ser (c.715C>T) is classified Uncertain significance in ALDOA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely pathogenic (0.9924); Very rare (popmax 0.00407%, nfe); Associated with glycogen storage disease due to aldolase A deficiency.

What condition is associated with ALDOA p.Pro239Ser (c.715C>T)?

ALDOA p.Pro239Ser (c.715C>T) is associated with glycogen storage disease due to aldolase A deficiency (ClinVar).

How common is ALDOA p.Pro239Ser (c.715C>T) in the general population?

ALDOA p.Pro239Ser (c.715C>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

What do computational predictors say about ALDOA p.Pro239Ser (c.715C>T)?

AlphaMissense predicts likely pathogenic (score 0.9924) — an in-silico prediction, not a clinical call.

ALDOA p.Pro239Ser

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.715C>T · VCV4077902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease due to aldolase A deficiency

Computational evidence

Protein change
AlphaMissense	0.9924	likely pathogenic
REVEL	0.979	strongly pathogenic-leaning
SaProt	LLR -13.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6	GERP 0.84, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,311 bp · p 0.028 · regional, not allelic
Overall
CADD	26.9	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 P185S vs ClinVar P239S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00407% European (non-Finnish) · 48/1,180,038 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00304% 49/1,614,068 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,584
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Pro239Ser
Coding: c.715C>T
Type: single nucleotide variant
Location: chr16:30069318 (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-pro239ser (accessed [today's date]).

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