Is CHUK p.Ile132Val (c.394A>G) pathogenic?

CHUK p.Ile132Val (c.394A>G) is classified Uncertain significance in CHUK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.1606); Very rare (popmax 0.000257%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHUK p.Ile132Val (c.394A>G)?

CHUK p.Ile132Val (c.394A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHUK p.Ile132Val (c.394A>G) in the general population?

CHUK p.Ile132Val (c.394A>G) is very rare (popmax 0.000257%, nfe) (gnomAD).

What do computational predictors say about CHUK p.Ile132Val (c.394A>G)?

AlphaMissense predicts likely benign (score 0.1606) — an in-silico prediction, not a clinical call.

CHUK p.Ile132Val

c.394A>G · VCV4228794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1606	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 11 kb · p 3.1e-13 · regional, not allelic
Overall
CADD	22.3	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 0.000257% European (non-Finnish) · 3/1,168,998 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000207% 3/1,449,468 alleles · very rare

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: CHUK
Protein: p.Ile132Val
Coding: c.394A>G
MANE Select: NM_001278
Type: single nucleotide variant
Location: chr10:100220668 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 84.41 · 5 PDB
Residue 132: the protein kinase domain

Full CHUK 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

CHUK p.Arg365Gln Uncertain significance ★★ ⚠ same condition
CHUK p.Arg424Cys Uncertain significance ★★ ⚠ same condition
CHUK p.Arg563Cys Uncertain significance ★★ ⚠ same condition
CHUK p.Arg563His Uncertain significance ★★ ⚠ same condition
CHUK p.Gln226Pro Uncertain significance ★★ ⚠ same condition
CHUK p.His520Arg Uncertain significance ★★ ⚠ same condition
CHUK p.Lys512Arg Uncertain significance ★★ ⚠ same condition
CHUK p.Met17Ile 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/chuk-p-ile132val (accessed [today's date]).

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