Is ALDOB p.Lys101fs (c.302del) pathogenic?

ALDOB p.Lys101fs (c.302del) is classified Pathogenic/Likely pathogenic in ALDOB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-21). Very rare (popmax 0.00119%, nfe); Associated with hereditary fructose intolerance.

What condition is associated with ALDOB p.Lys101fs (c.302del)?

ALDOB p.Lys101fs (c.302del) is associated with hereditary fructose intolerance, inborn errors of metabolism (ClinVar).

How common is ALDOB p.Lys101fs (c.302del) in the general population?

ALDOB p.Lys101fs (c.302del) is very rare (popmax 0.00119%, nfe) (gnomAD).

How is Hereditary fructose intolerance inherited?

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

ALDOB p.Lys101fs

c.302del · rs974582114 · VCV595944

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

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 -0.08	GERP -0.96, phastCons 0.56
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,180,036 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000867% 14/1,614,018 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.Lys101fs
Coding: c.302del
MANE Select: NM_000035
dbSNP: rs974582114
Type: Deletion
Location: chr9:101429777 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB

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

Also linked: inborn errors of metabolism

For Hereditary fructose intolerance (Orphanet):

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

Similar variants

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
ALDOB p.Leu84fs Pathogenic/Likely pathogenic ★★ same condition
ALDOB c.324+1del 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-lys101fs (accessed [today's date]).

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