Is ALDOA p.Gln329His (c.987G>C) pathogenic?

ALDOA p.Gln329His (c.987G>C) is classified Uncertain significance in ALDOA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-01). AlphaMissense: likely pathogenic (0.9908); Very rare (popmax 8.47e-05%, nfe).

How common is ALDOA p.Gln329His (c.987G>C) in the general population?

ALDOA p.Gln329His (c.987G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ALDOA p.Gln329His (c.987G>C)?

AlphaMissense predicts likely pathogenic (score 0.9908) — an in-silico prediction, not a clinical call.

ALDOA p.Gln329His

c.987G>C · rs1596816248 · VCV808029

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9908 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9908	likely pathogenic
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -13.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,311 bp · p 0.028 · regional, not allelic
Overall
CADD	28.8	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 Q275H vs ClinVar Q329H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,044 alleles

Overall 6.84e-05% 1/1,461,856 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
Protein: p.Gln329His
Coding: c.987G>C
MANE Select: NM_001243177
dbSNP: rs1596816248
Type: single nucleotide variant
Location: chr16:30069855 (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 329: a UniProt-annotated variant site (in gsd12); an α-helix

Full ALDOA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALDOA p.Ala334Val Pathogenic/Likely pathogenic ★★ same type
ALDOA c.274+5G>A Uncertain significance ★★ same type
ALDOA p.Ala142Val Uncertain significance ★★ same type
ALDOA p.Ala217Thr Uncertain significance ★★ same type
ALDOA p.Ala310Val Uncertain significance ★★ same type
ALDOA p.Ala377Ser Uncertain significance ★★ same type
ALDOA p.Ala74Thr Uncertain significance ★★ same type
ALDOA p.Arg146Cys Uncertain significance ★★ same type

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-gln329his (accessed [today's date]).

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