Is ALDOB p.Val249Ile (c.745G>A) pathogenic?

ALDOB p.Val249Ile (c.745G>A) is classified Uncertain significance in ALDOB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.0979); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALDOB p.Val249Ile (c.745G>A)?

ALDOB p.Val249Ile (c.745G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ALDOB p.Val249Ile (c.745G>A) in the general population?

ALDOB p.Val249Ile (c.745G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALDOB p.Val249Ile (c.745G>A)?

AlphaMissense predicts likely benign (score 0.0979) — an in-silico prediction, not a clinical call.

ALDOB p.Val249Ile

c.745G>A · rs2490120286 · VCV2232725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0979	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -7.03	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 6	GERP 2.9, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 9,075 bp · p 0.00067 · regional, not allelic
Overall
CADD	20.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALDOB
Protein: p.Val249Ile
Coding: c.745G>A
MANE Select: NM_000035
dbSNP: rs2490120286
Type: single nucleotide variant
Location: chr9:101425507 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 249: an α-helix

Full ALDOB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALDOB p.Tyr85Ter Pathogenic ★★ same condition
ALDOB p.Ala114Val Uncertain significance ★★ ⚠ same condition
ALDOB p.Ala256Ser Uncertain significance ★★ ⚠ same condition
ALDOB p.Arg56Cys Uncertain significance ★★ ⚠ same condition
ALDOB p.Arg60Gln Uncertain significance ★★ ⚠ same condition
ALDOB p.Asn285His Uncertain significance ★★ ⚠ same condition
ALDOB p.Gly112Arg Uncertain significance ★★ ⚠ same condition
ALDOB p.Gly118Arg Uncertain significance ★★ ⚠ 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-val249ile (accessed [today's date]).

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