Is ALDOB p.Arg304= (c.912G>C) pathogenic?

ALDOB p.Arg304= (c.912G>C) is classified Likely benign in ALDOB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-17). Very rare (popmax 0.0011%, sas); Associated with hereditary fructose intolerance.

What condition is associated with ALDOB p.Arg304= (c.912G>C)?

ALDOB p.Arg304= (c.912G>C) is associated with hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Arg304= (c.912G>C) in the general population?

ALDOB p.Arg304= (c.912G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Hereditary fructose intolerance inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ALDOB p.Arg304=

c.912G>C · rs1588170091 · VCV1101575

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hereditary fructose intolerance

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 0.11	GERP -1.9, phastCons 0.93
Overall
CADD	9.772	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,070 alleles

Overall 6.84e-05% 1/1,461,874 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: ALDOB
Protein: p.Arg304=
Coding: c.912G>C
MANE Select: NM_000035
dbSNP: rs1588170091
Type: single nucleotide variant
Location: chr9:101424930 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 304: a UniProt-annotated variant site (in hfi; 100-fold decrease in catalytic efficiency for substrates f1,6bp and f1p); a UniProt-annotated variant site (in hfi; turkey; 4800-fold decrease in catalytic efficiency for f1,6bp and inactive with f1p); a binding site; an α-helix

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

Disease context

hereditary fructose intolerance — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary fructose intolerance (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ALDOB p.Arg304Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ALDOB p.Arg304Trp Uncertain significance ★ ⚠ same residue
ALDOB p.Arg304Pro Uncertain significance ★ ⚠ same residue
ALDOB c.113-1G>C Pathogenic/Likely pathogenic ★★ same condition
ALDOB c.324+1G>A Pathogenic ★★ same condition
ALDOB c.324+2T>A Pathogenic ★★ same condition
ALDOB c.379+1G>A Likely pathogenic ★★ same condition
ALDOB c.379+1G>T Pathogenic/Likely pathogenic ★★ 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/aldob-p-arg304 (accessed [today's date]).

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