Is ALDOB p.Arg46fs (c.136del) pathogenic?

ALDOB p.Arg46fs (c.136del) is classified Pathogenic in ALDOB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). Absent from gnomAD; Associated with hereditary fructose intolerance.

What condition is associated with ALDOB p.Arg46fs (c.136del)?

ALDOB p.Arg46fs (c.136del) is associated with hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Arg46fs (c.136del) in the general population?

ALDOB p.Arg46fs (c.136del) is absent from gnomAD (gnomAD).

How is Hereditary fructose intolerance inherited?

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

ALDOB p.Arg46fs

c.136del · rs2490129062 · VCV2707586

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary fructose intolerance

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALDOB
Protein: p.Arg46fs
Coding: c.136del
MANE Select: NM_000035
dbSNP: rs2490129062
Type: Deletion
Location: chr9:101429943 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 46: a UniProt-annotated variant site (in hfi; reduced enzymatic activity); 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.Arg46Trp Uncertain significance ★★ ⚠ same residue
ALDOB p.Arg46Lys Uncertain significance ★ ⚠ same residue
ALDOB c.113-1_115del Pathogenic/Likely pathogenic ★★ same condition
ALDOB c.541-277_651del Likely pathogenic ★★ same condition
ALDOB p.Asp141fs Pathogenic/Likely pathogenic ★★ same condition
ALDOB p.Glu15fs Pathogenic/Likely pathogenic ★★ same condition
ALDOB p.Glu225fs Pathogenic/Likely pathogenic ★★ same condition
ALDOB p.Leu289fs 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-arg46fs (accessed [today's date]).

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