Is ITK p.Asp127fs (c.380del) pathogenic?

ITK p.Asp127fs (c.380del) is classified Pathogenic in ITK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-21). Absent from gnomAD; Associated with lymphoproliferative syndrome 1.

What condition is associated with ITK p.Asp127fs (c.380del)?

ITK p.Asp127fs (c.380del) is associated with lymphoproliferative syndrome 1 (ClinVar).

How common is ITK p.Asp127fs (c.380del) in the general population?

ITK p.Asp127fs (c.380del) is absent from gnomAD (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 p.Asp127fs

c.380del · rs2480559806 · VCV2088804

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

lymphoproliferative syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ITK
Protein: p.Asp127fs
Coding: c.380del
MANE Select: NM_005546
dbSNP: rs2480559806
Type: Deletion
Location: chr5:157214245 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.82 · 37 PDB
Residue 127: a β-strand

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.Gly555fs Pathogenic ★ same condition
ITK c.986-5_986-2del Conflicting classifications of pathogenicity ★ same condition
ITK c.243+14del Likely benign ★ 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-p-asp127fs (accessed [today's date]).

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