Is CHUK p.Ala11Val (c.32C>T) pathogenic?

CHUK p.Ala11Val (c.32C>T) is classified Conflicting classifications of pathogenicity in CHUK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-18). AlphaMissense: likely benign (0.1009); Rare (popmax 0.136%, eas); Associated with Inborn genetic diseases.

What condition is associated with CHUK p.Ala11Val (c.32C>T)?

CHUK p.Ala11Val (c.32C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHUK p.Ala11Val (c.32C>T) in the general population?

CHUK p.Ala11Val (c.32C>T) is rare (popmax 0.136%, eas) (gnomAD).

What do computational predictors say about CHUK p.Ala11Val (c.32C>T)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

CHUK p.Ala11Val

c.32C>T · rs766454749 · VCV1586846

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.136%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 0.88, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 76 bp · p 0.44 · regional, not allelic
Overall
CADD	23.7	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 0.136% East Asian · 58/42,756 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0976%

Overall 0.00446% 70/1,570,814 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.136%	737
Remaining individualsnot grpmax-eligible	0.0164%	6,096
Admixed American	0.00182%	55,070
African / African-American	0.00135%	73,974

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.Ala11Val
Coding: c.32C>T
MANE Select: NM_001278
dbSNP: rs766454749
Type: single nucleotide variant
Location: chr10:100229501 (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.Ala11= Likely benign ★ same residue
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

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-ala11val (accessed [today's date]).

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