Is ALDOB p.Pro246= (c.738A>G) pathogenic?

ALDOB p.Pro246= (c.738A>G) is classified Likely benign in ALDOB (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-06). Very rare (popmax 0.00892%, eas); Associated with hereditary fructose intolerance.

What condition is associated with ALDOB p.Pro246= (c.738A>G)?

ALDOB p.Pro246= (c.738A>G) is associated with hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Pro246= (c.738A>G) in the general population?

ALDOB p.Pro246= (c.738A>G) is very rare (popmax 0.00892%, eas) (gnomAD).

How is Hereditary fructose intolerance inherited?

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

ALDOB p.Pro246=

c.738A>G · rs781139407 · VCV1160257

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

hereditary fructose intolerance

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -5.9
Overall
CADD	8.595	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,860 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000479% 7/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,215
European (non-Finnish)	0.000254%	393,343

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.Pro246=
Coding: c.738A>G
MANE Select: NM_000035
dbSNP: rs781139407
Type: single nucleotide variant
Location: chr9:101425514 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 246: 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 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-pro246 (accessed [today's date]).

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