Is CHUK p.Arg57Ter (c.169C>T) pathogenic?

CHUK p.Arg57Ter (c.169C>T) is classified Likely pathogenic in CHUK (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-30). Very rare (popmax 0.0033%, sas); Associated with CHUK-related disorder.

What condition is associated with CHUK p.Arg57Ter (c.169C>T)?

CHUK p.Arg57Ter (c.169C>T) is associated with CHUK-related disorder (ClinVar).

How common is CHUK p.Arg57Ter (c.169C>T) in the general population?

CHUK p.Arg57Ter (c.169C>T) is very rare (popmax 0.0033%, sas) (gnomAD).

CHUK p.Arg57Ter

c.169C>T · VCV4909157

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Conditions

CHUK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 21
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP -0.15, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/90,942 alleles

Filtering AF 0.000876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000436% 7/1,606,896 alleles · very rare exomes 7/1,454,964 · genomes 0/151,932 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,314
European (non-Finnish)	0.000341%	293,457

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.Arg57Ter
Coding: c.169C>T
MANE Select: NM_001278
Type: single nucleotide variant
Location: chr10:100225954 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 84.41 · 5 PDB
Residue 57: the protein kinase domain

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

Disease context

CHUK-related disorder

Similar variants

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
CHUK p.Lys512Arg 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-arg57ter (accessed [today's date]).

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