Is CSK p.Glu417Asp (c.1251A>C) pathogenic?

CSK p.Glu417Asp (c.1251A>C) is classified Uncertain significance in CSK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.0748); Absent from gnomAD v4.1.

How common is CSK p.Glu417Asp (c.1251A>C) in the general population?

CSK p.Glu417Asp (c.1251A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSK p.Glu417Asp (c.1251A>C)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

CSK p.Glu417Asp

c.1251A>C · VCV3836724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.41	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 -0.22	GERP -4.8, phastCons 0.046
Regional constraint	o/e 0.66	unconstrained · MANE · 462 bp · p 0.00084 · regional, not allelic
Overall
CADD	8.629	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Glu417Asp
Coding: c.1251A>C
MANE Select: NM_004383
Type: single nucleotide variant
Location: chr15:74802411 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.57 · 6 PDB
Residue 417: the protein kinase domain; an α-helix

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-glu417asp (accessed [today's date]).

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