Is CHUK p.Val155Ala (c.464T>C) pathogenic?

CHUK p.Val155Ala (c.464T>C) is classified Benign/Likely benign in CHUK (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0832); Common (popmax 5.57%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CHUK p.Val155Ala (c.464T>C)?

AlphaMissense predicts likely benign (score 0.0832) — an in-silico prediction, not a clinical call.

CHUK p.Val155Ala

Q: How common is CHUK p.Val155Ala (c.464T>C) in the general population?

CHUK p.Val155Ala (c.464T>C) is common (popmax 5.57%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.464T>C · rs2230803 · VCV1288665

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0832 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.57%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0832	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -7.28	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 3.5	GERP -3.7, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 11 kb · p 3.1e-13 · regional, not allelic
Overall
CADD	12.36	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 5.57% East Asian · 2,492/44,758 alleles

Filtering AF 5.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.31%

Overall 0.566% 9,101/1,609,226 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	5.57%	18
South Asian	4.98%	20
Remaining individualsnot grpmax-eligible	0.887%	113
Middle Eastern	0.811%	123
Ashkenazi Jewishnot grpmax-eligible	0.683%	146
Amishnot grpmax-eligible	0.219%	456
Admixed American	0.152%	660
European (non-Finnish)	0.0967%	1,034
African / African-American	0.0534%	1,874
Finnishnot grpmax-eligible	0.00469%	21,300

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.Val155Ala
Coding: c.464T>C
MANE Select: NM_001278
dbSNP: rs2230803
Type: single nucleotide variant
Location: chr10:100220598 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 84.41 · 5 PDB
Residue 155: 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-val155ala (accessed [today's date]).

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