Is CHUK p.Leu423= (c.1267C>T) pathogenic?

CHUK p.Leu423= (c.1267C>T) is classified Likely benign in CHUK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). Very rare (popmax 0.00153%, nfe).

How common is CHUK p.Leu423= (c.1267C>T) in the general population?

CHUK p.Leu423= (c.1267C>T) is very rare (popmax 0.00153%, nfe) (gnomAD).

CHUK p.Leu423=

c.1267C>T · VCV3614355

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

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 2.7	GERP 1.9, phastCons 1
Overall
CADD	8.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,179,840 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,613,806 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.Leu423=
Coding: c.1267C>T
MANE Select: NM_001278
Type: single nucleotide variant
Location: chr10:100205164 (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.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-leu423 (accessed [today's date]).

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