Is ALDOA c.786+2T>C pathogenic?

ALDOA c.786+2T>C is classified Likely pathogenic in ALDOA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). Very rare (popmax 0.00267%, afr); Associated with glycogen storage disease due to aldolase A deficiency.

What condition is associated with ALDOA c.786+2T>C?

ALDOA c.786+2T>C is associated with glycogen storage disease due to aldolase A deficiency (ClinVar).

How common is ALDOA c.786+2T>C in the general population?

ALDOA c.786+2T>C is very rare (popmax 0.00267%, afr) (gnomAD).

ALDOA c.786+2T>C

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.

rs892947296 · VCV2956786

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

glycogen storage disease due to aldolase A deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.96	donor loss · deltas
Pangolin	Δ0.90	loss · gain 0.79 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Non-coding constraint	Z 1.29	1 kb window · o/e 0.92 · regional · uncalibrated
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,802 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00132% 2/151,896 alleles · very 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
Coding: c.786+2T>C
MANE Select: NM_001243177
dbSNP: rs892947296
Type: single nucleotide variant
Location: chr16:30069391 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.53 · 8 PDB

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.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
ALDOA p.Arg146Cys 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-c-786-plus-2t-c (accessed [today's date]).

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