Is CHUK p.Arg493Ser (c.1479A>T) pathogenic?

CHUK p.Arg493Ser (c.1479A>T) is classified Uncertain significance in CHUK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely pathogenic (0.8202); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHUK p.Arg493Ser (c.1479A>T)?

CHUK p.Arg493Ser (c.1479A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHUK p.Arg493Ser (c.1479A>T) in the general population?

CHUK p.Arg493Ser (c.1479A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHUK p.Arg493Ser (c.1479A>T)?

AlphaMissense predicts likely pathogenic (score 0.8202) — an in-silico prediction, not a clinical call.

CHUK p.Arg493Ser

c.1479A>T · VCV3833358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8202 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8202	likely pathogenic
REVEL	0.107	moderately benign-leaning
SaProt	LLR -4.47	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
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 0.79	unconstrained · MANE · 16 kb · p 3.3e-05 · regional, not allelic
Overall
CADD	23.6	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

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: CHUK
Protein: p.Arg493Ser
Coding: c.1479A>T
MANE Select: NM_001278
Type: single nucleotide variant
Location: chr10:100204534 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 84.41 · 5 PDB

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-arg493ser (accessed [today's date]).

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