Is ITK c.243+14del pathogenic?

ITK c.243+14del is classified Likely benign in ITK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). Very rare (popmax 0.00544%, afr); Associated with lymphoproliferative syndrome 1.

What condition is associated with ITK c.243+14del?

ITK c.243+14del is associated with lymphoproliferative syndrome 1 (ClinVar).

How common is ITK c.243+14del in the general population?

ITK c.243+14del is very rare (popmax 0.00544%, afr) (gnomAD).

How is Combined immunodeficiency due to ITK deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ITK c.243+14del

rs759525228 · VCV3015962

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00544%, afr)

Conditions

lymphoproliferative syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +14	near-intronic (+14 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.27	GERP -2.2
Non-coding constraint	Z 0.66	1 kb window · o/e 0.94 · regional · uncalibrated
Overall
CADD	7.654	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00544% African / African-American · 4/73,586 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.000258% 4/1,548,156 alleles · very rare

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: ITK
Coding: c.243+14del
MANE Select: NM_005546
dbSNP: rs759525228
Type: Deletion
Location: chr5:157209006 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.82 · 37 PDB

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

Disease context

lymphoproliferative syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to ITK deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

ITK p.Arg44fs Likely pathogenic ★ same condition
ITK p.Asp127fs Pathogenic ★ same condition
ITK p.Gly555fs Pathogenic ★ same condition
ITK c.986-5_986-2del Conflicting classifications of pathogenicity ★ same condition
ITK c.852-7_852-4del Likely benign ★ same condition
ITK c.851+5G>A Uncertain significance ★★ same condition
ITK p.Ala191Thr Uncertain significance ★★ ⚠ same condition
ITK p.Ala261Thr 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/itk-c-243-plus-14del (accessed [today's date]).

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