Is ALDOB p.Ala319Val (c.956C>T) pathogenic?

ALDOB p.Ala319Val (c.956C>T) is classified Uncertain significance in ALDOB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-31). AlphaMissense: likely benign (0.0966); Ultra-rare (popmax 0.0171%, mid); Associated with hereditary fructose intolerance.

What condition is associated with ALDOB p.Ala319Val (c.956C>T)?

ALDOB p.Ala319Val (c.956C>T) is associated with hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Ala319Val (c.956C>T) in the general population?

ALDOB p.Ala319Val (c.956C>T) is ultra-rare (popmax 0.0171%, mid) (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.Ala319Val (c.956C>T)?

AlphaMissense predicts likely benign (score 0.0966) — an in-silico prediction, not a clinical call.

ALDOB p.Ala319Val

c.956C>T · rs755508323 · VCV364308

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0966 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary fructose intolerance

Computational evidence

Protein change
AlphaMissense	0.0966	likely benign
REVEL	0.381	indeterminate
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP -1.9, phastCons 0.99
Regional constraint	o/e 1.16	unconstrained · MANE · 9,075 bp · p 0.00067 · regional, not allelic
Overall
CADD	19.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0171% Middle Eastern · 1/5,844 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00304% 49/1,613,790 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0171%	5,844
Admixed American	0.015%	6,668
Remaining individualsnot grpmax-eligible	0.0048%	20,818
European (non-Finnish)	0.00305%	32,779

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.Ala319Val
Coding: c.956C>T
MANE Select: NM_000035
dbSNP: rs755508323
Type: single nucleotide variant
Location: chr9:101424886 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 319: 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.Ala319_Ala332del Likely pathogenic 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
ALDOB c.380-2A>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-ala319val (accessed [today's date]).

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