Is ALDOB p.Val77fs (c.227dup) pathogenic?

ALDOB p.Val77fs (c.227dup) is classified Pathogenic in ALDOB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-03). Ultra-rare (gnomAD MAF 1.679e-06); Associated with hereditary fructose intolerance.

What condition is associated with ALDOB p.Val77fs (c.227dup)?

ALDOB p.Val77fs (c.227dup) is associated with hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Val77fs (c.227dup) in the general population?

ALDOB p.Val77fs (c.227dup) is ultra-rare (gnomAD MAF 1.679e-06) (gnomAD).

How is Hereditary fructose intolerance inherited?

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

ALDOB p.Val77fs

c.227dup · rs2118362340 · VCV1379379

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 1.679e-06)

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 -2.9	GERP -3.9

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

Population frequency

dbSNP / gnomAD

Global frequency 0.000168% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: ALDOB
Protein: p.Val77fs
Coding: c.227dup
MANE Select: NM_000035
dbSNP: rs2118362340
Type: Duplication
Location: chr9:101429851 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 77: a β-strand

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.Val77= Likely benign ★ same residue
ALDOB p.Thr255fs Pathogenic ★★ same condition
ALDOB p.Glu53fs Pathogenic ★ same condition
ALDOB p.Val104_Ile107dup Uncertain significance ★ same condition
ALDOB c.625-9_625-7dup Likely benign ★ same condition
ALDOB p.His238fs Likely pathogenic same condition
ALDOB p.Leu229_Lys230insMetLeu Likely pathogenic same condition
ALDOB p.Trp314fs 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-val77fs (accessed [today's date]).

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