Is CHUK p.Val268Ile (c.802G>A) pathogenic?

CHUK p.Val268Ile (c.802G>A) is classified Benign/Likely benign in CHUK (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0575); Common (popmax 75.4%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CHUK p.Val268Ile (c.802G>A)?

AlphaMissense predicts likely benign (score 0.0575) — an in-silico prediction, not a clinical call.

CHUK p.Val268Ile

Q: How common is CHUK p.Val268Ile (c.802G>A) in the general population?

CHUK p.Val268Ile (c.802G>A) is common (popmax 75.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.802G>A · rs2230804 · VCV1221248

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0575 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 75.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0575	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -4.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.85	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 3.5	GERP 0.75, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 11 kb · p 3.1e-13 · regional, not allelic
Overall
CADD	16.85	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

Grpmax group 75.4% African / African-American · 56,318/74,728 alleles

Filtering AF 74.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 74.6%

Overall 51% 818,171/1,605,460 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	75.4%	1
Amishnot grpmax-eligible	63.8%	2
European (non-Finnish)	51.9%	2
Remaining individualsnot grpmax-eligible	51.5%	2
East Asian	48.1%	2
Middle Eastern	47.2%	2
Finnishnot grpmax-eligible	46.3%	2
Ashkenazi Jewishnot grpmax-eligible	42.5%	2
Admixed American	39.8%	3
South Asian	33.7%	3

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.Val268Ile
Coding: c.802G>A
MANE Select: NM_001278
dbSNP: rs2230804
Type: single nucleotide variant
Location: chr10:100218126 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 84.41 · 5 PDB
Residue 268: the protein kinase domain; a UniProt-annotated variant site (in)

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-val268ile (accessed [today's date]).

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