Is CSK p.Tyr97Cys (c.290A>G) pathogenic?

CSK p.Tyr97Cys (c.290A>G) is classified Likely benign in CSK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.0717); Very rare (popmax 0.00167%, amr).

How common is CSK p.Tyr97Cys (c.290A>G) in the general population?

CSK p.Tyr97Cys (c.290A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CSK p.Tyr97Cys (c.290A>G)?

AlphaMissense predicts likely benign (score 0.0717) — an in-silico prediction, not a clinical call.

CSK p.Tyr97Cys

c.290A>G · VCV3497598

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0717 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0717	likely benign
REVEL	0.315	indeterminate
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.3	GERP 0.65, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 3,413 bp · p 1e-25 · regional, not allelic
Overall
CADD	22.0	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 0.00167% Admixed American · 1/59,978 alleles

Overall 0.000124% 2/1,611,472 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,978
African / African-American	0.00134%	74,798

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: CSK
Protein: p.Tyr97Cys
Coding: c.290A>G
MANE Select: NM_004383
Type: single nucleotide variant
Location: chr15:74799319 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.57 · 6 PDB
Residue 97: the sh2 domain

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-tyr97cys (accessed [today's date]).

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