Is ALDOB p.Leu63Phe (c.187C>T) pathogenic?

ALDOB p.Leu63Phe (c.187C>T) is classified Uncertain significance in ALDOB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-09-04). AlphaMissense: ambiguous (0.5164); Ultra-rare (popmax 0.0133%, amr); Associated with hereditary fructose intolerance.

What condition is associated with ALDOB p.Leu63Phe (c.187C>T)?

ALDOB p.Leu63Phe (c.187C>T) is associated with hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Leu63Phe (c.187C>T) in the general population?

ALDOB p.Leu63Phe (c.187C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

How is Hereditary fructose intolerance inherited?

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

What do computational predictors say about ALDOB p.Leu63Phe (c.187C>T)?

AlphaMissense predicts ambiguous (score 0.5164) — an in-silico prediction, not a clinical call.

ALDOB p.Leu63Phe

c.187C>T · rs780352710 · VCV991610

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5164 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary fructose intolerance

Computational evidence

Protein change
AlphaMissense	0.5164	ambiguous
REVEL	0.903	moderately pathogenic-leaning
SaProt	LLR -10.49	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 9,075 bp · p 0.00067 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,998 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000496% 8/1,613,998 alleles · ultra-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.Leu63Phe
Coding: c.187C>T
MANE Select: NM_000035
dbSNP: rs780352710
Type: single nucleotide variant
Location: chr9:101429892 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 63: 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-leu63phe (accessed [today's date]).

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