Is ALDOB p.Arg4Ter (c.10C>T) pathogenic?

ALDOB p.Arg4Ter (c.10C>T) is classified Pathogenic in ALDOB (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-05-27). Ultra-rare (popmax 0.0134%, eas); Associated with ALDOB-related disorder.

What condition is associated with ALDOB p.Arg4Ter (c.10C>T)?

ALDOB p.Arg4Ter (c.10C>T) is associated with ALDOB-related disorder, hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Arg4Ter (c.10C>T) in the general population?

ALDOB p.Arg4Ter (c.10C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

ALDOB p.Arg4Ter

c.10C>T · rs118204428 · VCV471

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

ALDOB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.055, phastCons 1
Overall
CADD	41.0	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 0.0134% East Asian · 6/44,864 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00123% 18/1,461,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,477
South Asian	0.00329%	30,351
African / African-American	0.00267%	37,486
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000424%	235,856

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.Arg4Ter
Coding: c.10C>T
MANE Select: NM_000035
dbSNP: rs118204428
Type: single nucleotide variant
Location: chr9:101430878 (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

ALDOB-related disorder

Also linked: hereditary fructose intolerance

Similar variants

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
ALDOB c.380-1G>A Pathogenic/Likely pathogenic ★★ same condition
ALDOB c.380-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALDOB c.625-2A>G 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-arg4ter (accessed [today's date]).

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