Is ALDOA p.Ala142= (c.426G>A) pathogenic?

ALDOA p.Ala142= (c.426G>A) is classified Likely benign in ALDOA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). Ultra-rare (popmax 0.07%, amr); Associated with glycogen storage disease due to aldolase A deficiency.

What condition is associated with ALDOA p.Ala142= (c.426G>A)?

ALDOA p.Ala142= (c.426G>A) is associated with glycogen storage disease due to aldolase A deficiency (ClinVar).

How common is ALDOA p.Ala142= (c.426G>A) in the general population?

ALDOA p.Ala142= (c.426G>A) is ultra-rare (popmax 0.07%, amr) (gnomAD).

ALDOA p.Ala142=

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.426G>A · rs772550893 · VCV1580647

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.07%, amr)

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 -4.5	GERP -3.9
Overall
CADD	5.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.07% Admixed American · 42/59,976 alleles

Filtering AF 0.0532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0473%

Overall 0.00341% 55/1,613,982 alleles · ultra-rare exomes 28/1,461,850 · genomes 27/152,132 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.07%	1,428
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.000932%	107,277

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.Ala142=
Coding: c.426G>A
MANE Select: NM_001243177
dbSNP: rs772550893
Type: single nucleotide variant
Location: chr16:30067601 (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 142: a UniProt-annotated variant site (in)

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.Ala142Val Uncertain significance ★★ same residue
ALDOA p.Ala334Val Pathogenic/Likely pathogenic ★★ same condition
ALDOA c.274+5G>A 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-p-ala142 (accessed [today's date]).

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