Is ALDOB p.Ala256Ser (c.766G>T) pathogenic?

ALDOB p.Ala256Ser (c.766G>T) is classified Uncertain significance in ALDOB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-24). AlphaMissense: likely benign (0.1793); Very rare (popmax 0.00799%, afr); Associated with Inborn genetic diseases.

What condition is associated with ALDOB p.Ala256Ser (c.766G>T)?

ALDOB p.Ala256Ser (c.766G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALDOB p.Ala256Ser (c.766G>T) in the general population?

ALDOB p.Ala256Ser (c.766G>T) is very rare (popmax 0.00799%, afr) (gnomAD).

What do computational predictors say about ALDOB p.Ala256Ser (c.766G>T)?

AlphaMissense predicts likely benign (score 0.1793) — an in-silico prediction, not a clinical call.

ALDOB p.Ala256Ser

c.766G>T · rs201551409 · VCV502283

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1793 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00799%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1793	likely benign
REVEL	0.491	indeterminate
SaProt	LLR -9.81	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 4	GERP 2.1, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 9,075 bp · p 0.00067 · regional, not allelic
Overall
CADD	22.8	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 0.00799% African / African-American · 6/75,058 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000434% 7/1,614,176 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00799%	12,510
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Ala256Ser
Coding: c.766G>T
MANE Select: NM_000035
dbSNP: rs201551409
Type: single nucleotide variant
Location: chr9:101425486 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.12 · 4 PDB
Residue 256: 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.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
ALDOB p.Gly76Ser 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-ala256ser (accessed [today's date]).

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