Is ALDOA p.Ala142Val (c.425C>T) pathogenic?

ALDOA p.Ala142Val (c.425C>T) is classified Uncertain significance in ALDOA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-14). AlphaMissense: ambiguous (0.4413); Very rare (popmax 0.00333%, amr); Associated with glycogen storage disease due to aldolase A deficiency.

What condition is associated with ALDOA p.Ala142Val (c.425C>T)?

ALDOA p.Ala142Val (c.425C>T) is associated with glycogen storage disease due to aldolase A deficiency (ClinVar).

How common is ALDOA p.Ala142Val (c.425C>T) in the general population?

ALDOA p.Ala142Val (c.425C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ALDOA p.Ala142Val (c.425C>T)?

AlphaMissense predicts ambiguous (score 0.4413) — an in-silico prediction, not a clinical call.

ALDOA p.Ala142Val

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.425C>T · rs1385792025 · VCV1934970

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

glycogen storage disease due to aldolase A deficiency

Computational evidence

Protein change
AlphaMissense	0.4413	ambiguous
REVEL	0.392	indeterminate
SaProt	LLR -10.48	damaging
Splicing
SpliceAI	Δ0.38	donor gain · deltas
Pangolin	Δ0.21	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 0.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,311 bp · p 0.028 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A88V vs ClinVar A142V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00062% 10/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,996
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000593%	168,577

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.Ala142Val
Coding: c.425C>T
MANE Select: NM_001243177
dbSNP: rs1385792025
Type: single nucleotide variant
Location: chr16:30067600 (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.Ala142= Likely benign ★ 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-ala142val (accessed [today's date]).

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