Is ALDOB p.Ala338Val (c.1013C>T) pathogenic?

ALDOB p.Ala338Val (c.1013C>T) is classified Pathogenic/Likely pathogenic in ALDOB (ClinVar, Multiple submitters, 20 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.9407); Ultra-rare (popmax 0.0825%, mid); Associated with ALDOB-related disorder.

What condition is associated with ALDOB p.Ala338Val (c.1013C>T)?

ALDOB p.Ala338Val (c.1013C>T) is associated with ALDOB-related disorder, hereditary fructose intolerance (ClinVar).

How common is ALDOB p.Ala338Val (c.1013C>T) in the general population?

ALDOB p.Ala338Val (c.1013C>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about ALDOB p.Ala338Val (c.1013C>T)?

AlphaMissense predicts likely pathogenic (score 0.9407) — an in-silico prediction, not a clinical call.

ALDOB p.Ala338Val

c.1013C>T · rs77718928 · VCV188739

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 20 submitters

AlphaMissense

likely pathogenic

0.9407 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALDOB-related disorder

Computational evidence

Protein change
AlphaMissense	0.9407	likely pathogenic ✓ concordant with ClinVar
REVEL	0.92	moderately pathogenic-leaning
SaProt	LLR -12.63	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 9,075 bp · p 0.00067 · regional, not allelic
Overall
CADD	29.1	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 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0375%

Overall 0.0083% 134/1,613,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
South Asian	0.0539%	1,857
African / African-American	0.0253%	3,949
Remaining individualsnot grpmax-eligible	0.0192%	5,208
East Asian	0.0134%	7,479
European (non-Finnish)	0.00347%	28,778
Admixed American	0.00167%	59,982
Finnishnot grpmax-eligible	0.00156%	64,002

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.Ala338Val
Coding: c.1013C>T
MANE Select: NM_000035
dbSNP: rs77718928
Type: single nucleotide variant
Location: chr9:101421891 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 338: a UniProt-annotated variant site (in hfi; turkey and south europe); an α-helix

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 p.Ala338= Conflicting classifications of pathogenicity ★ 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-ala338val (accessed [today's date]).

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