Is ALDOB p.Ala163= (c.489T>A) pathogenic?

ALDOB p.Ala163= (c.489T>A) is classified Conflicting classifications of pathogenicity in ALDOB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-27). Ultra-rare (popmax 0.0626%, sas); Associated with hereditary fructose intolerance.

What condition is associated with ALDOB p.Ala163= (c.489T>A)?

ALDOB p.Ala163= (c.489T>A) is associated with hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Ala163= (c.489T>A) in the general population?

ALDOB p.Ala163= (c.489T>A) is ultra-rare (popmax 0.0626%, sas) (gnomAD).

How is Hereditary fructose intolerance inherited?

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

ALDOB p.Ala163=

c.489T>A · rs578048957 · VCV597757

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, sas)

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 -0.17	GERP -3.4, phastCons 0.009
Overall
CADD	5.534	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0626% South Asian · 57/91,090 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.00384% 62/1,614,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0626%	1,598
Remaining individualsnot grpmax-eligible	0.0048%	20,837
African / African-American	0.00133%	75,060
European (non-Finnish)	8.47e-05%	1,180,025

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.Ala163=
Coding: c.489T>A
MANE Select: NM_000035
dbSNP: rs578048957
Type: single nucleotide variant
Location: chr9:101427533 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 163: 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.Ala163Val Conflicting classifications of pathogenicity ★ ⚠ same residue
ALDOB p.Ala163Thr Uncertain significance ★★ ⚠ same residue
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

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-ala163 (accessed [today's date]).

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