Is CSK p.Ile264Val (c.790A>G) pathogenic?

CSK p.Ile264Val (c.790A>G) is classified Uncertain significance in CSK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely pathogenic (0.5867); Absent from gnomAD v4.1.

How common is CSK p.Ile264Val (c.790A>G) in the general population?

CSK p.Ile264Val (c.790A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSK p.Ile264Val (c.790A>G)?

AlphaMissense predicts likely pathogenic (score 0.5867) — an in-silico prediction, not a clinical call.

CSK p.Ile264Val

c.790A>G · VCV4656999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5867 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5867	likely pathogenic
REVEL	0.578	indeterminate
SaProt	LLR -9.19	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 3,413 bp · p 1e-25 · regional, not allelic
Overall
CADD	23.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSK
Protein: p.Ile264Val
Coding: c.790A>G
MANE Select: NM_004383
Type: single nucleotide variant
Location: chr15:74801079 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.57 · 6 PDB
Residue 264: the protein kinase domain; a β-strand

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

Similar variants

CSK p.Gly287Asp Benign ★★ same type
CSK p.Ala407Thr Uncertain significance ★ ⚠ same type
CSK p.Arg56Cys Uncertain significance ★ ⚠ same type
CSK p.Arg56His Uncertain significance ★ ⚠ same type
CSK p.Arg94Gln Uncertain significance ★ ⚠ same type
CSK p.Asn46Lys Uncertain significance ★ ⚠ same type
CSK p.Asn63Ser Uncertain significance ★ ⚠ same type
CSK p.Asp123Asn 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/csk-p-ile264val (accessed [today's date]).

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