Is CHUK p.Ser486Ile (c.1457G>T) pathogenic?

CHUK p.Ser486Ile (c.1457G>T) is classified Uncertain significance in CHUK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely pathogenic (0.9793); Absent from gnomAD v4.1.

How common is CHUK p.Ser486Ile (c.1457G>T) in the general population?

CHUK p.Ser486Ile (c.1457G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHUK p.Ser486Ile (c.1457G>T)?

AlphaMissense predicts likely pathogenic (score 0.9793) — an in-silico prediction, not a clinical call.

CHUK p.Ser486Ile

c.1457G>T · rs2493043019 · VCV2123939

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9793 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9793	likely pathogenic
REVEL	0.859	moderately pathogenic-leaning
SaProt	LLR -9.02	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 3.3e-05 · regional, not allelic
Overall
CADD	28.6	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.Ser486Ile
Coding: c.1457G>T
MANE Select: NM_001278
dbSNP: rs2493043019
Type: single nucleotide variant
Location: chr10:100204556 (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

Similar variants

CHUK p.Ser486= Benign ★★ same residue
CHUK p.Arg365Gln Uncertain significance ★★ ⚠ same type
CHUK p.Arg424Cys Uncertain significance ★★ ⚠ same type
CHUK p.Arg563Cys Uncertain significance ★★ ⚠ same type
CHUK p.Arg563His Uncertain significance ★★ ⚠ same type
CHUK p.Gln226Pro Uncertain significance ★★ ⚠ same type
CHUK p.Gly346Arg Uncertain significance ★★ ⚠ same type
CHUK p.His520Arg 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/chuk-p-ser486ile (accessed [today's date]).

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