Is ALDOB p.Cys336fs (c.1007_1008delinsT) pathogenic?

ALDOB p.Cys336fs (c.10071008delinsT) is classified Likely pathogenic in ALDOB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-13). Absent from gnomAD; Associated with hereditary fructose intolerance.

What condition is associated with ALDOB p.Cys336fs (c.1007_1008delinsT)?

ALDOB p.Cys336fs (c.1007_1008delinsT) is associated with hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Cys336fs (c.1007_1008delinsT) in the general population?

ALDOB p.Cys336fs (c.1007_1008delinsT) 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.Cys336fs

c.1007_1008delinsT · rs1831052831 · VCV2739775

Likely pathogenic Single submitter

Classification

Likely 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	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 0.2, 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.Cys336fs
Coding: c.1007_1008delinsT
MANE Select: NM_000035
dbSNP: rs1831052831
Type: Indel
Location: chr9:101421896 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 336: 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.Cys336= Likely benign ★ same residue
ALDOB c.1000-1_1006delinsTG Pathogenic/Likely pathogenic ★★ same condition
ALDOB c.541-277_651delinsATGGGTT Likely pathogenic ★ same condition
ALDOB p.Gln248fs Likely pathogenic ★ same condition
ALDOB p.Leu131fs Likely pathogenic ★ same condition
ALDOB p.Ser349fs Likely pathogenic same condition
ALDOB c.113-1_115del Pathogenic/Likely pathogenic ★★ same condition
ALDOB c.113-1G>C 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-cys336fs (accessed [today's date]).

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