Is ACOT4 p.Ala189= (c.567T>A) pathogenic?

ACOT4 p.Ala189= (c.567T>A) is classified Uncertain significance in ACOT4 (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with ACOT4 p.Ala189= (c.567T>A)?

ACOT4 p.Ala189= (c.567T>A) is associated with intellectual disability (ClinVar).

How common is ACOT4 p.Ala189= (c.567T>A) in the general population?

ACOT4 p.Ala189= (c.567T>A) is absent from gnomAD v4.1 (gnomAD).

ACOT4 p.Ala189=

c.567T>A · rs74553611 · VCV488645

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual disability

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.022	GERP -0.38, phastCons 0.94
Overall
CADD	9.393	PHRED · no single calibrated threshold — expert panels disagree

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: ACOT4
Protein: p.Ala189=
Coding: c.567T>A
MANE Select: NM_152331
dbSNP: rs74553611
Type: single nucleotide variant
Location: chr14:73593811 (GRCh38)
Gene constraint: LOEUF 1.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.47 · 1 PDB
Residue 189: a β-strand

Full ACOT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACOT4 p.Tyr190Cys Uncertain significance ⚠ same condition
ACOT4 p.Ala235Gly Uncertain significance ★ ⚠ same type
ACOT4 p.Ala235Thr Uncertain significance ★ ⚠ same type
ACOT4 p.Ala242Ser Uncertain significance ★ ⚠ same type
ACOT4 p.Ala242Val Uncertain significance ★ ⚠ same type
ACOT4 p.Ala372Gly Uncertain significance ★ ⚠ same type
ACOT4 p.Ala48Thr Uncertain significance ★ ⚠ same type
ACOT4 p.Ala65Thr Uncertain significance ★ ⚠ same type

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/acot4-p-ala189 (accessed [today's date]).

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