Is ITK p.Phe340Ser (c.1019T>C) pathogenic?

ITK p.Phe340Ser (c.1019T>C) is classified Likely benign in ITK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely benign (0.0667); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with ITK p.Phe340Ser (c.1019T>C)?

ITK p.Phe340Ser (c.1019T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ITK p.Phe340Ser (c.1019T>C) in the general population?

ITK p.Phe340Ser (c.1019T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ITK p.Phe340Ser (c.1019T>C)?

AlphaMissense predicts likely benign (score 0.0667) — an in-silico prediction, not a clinical call.

ITK p.Phe340Ser

c.1019T>C · rs1398830172 · VCV2469289

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0667 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0667	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -2.83	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 5.9	GERP 0.81, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 63 kb · p 2.1e-06 · regional, not allelic
Overall
CADD	17.76	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 0.00223% East Asian · 1/44,886 alleles

Overall 6.84e-05% 1/1,461,766 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
Protein: p.Phe340Ser
Coding: c.1019T>C
MANE Select: NM_005546
dbSNP: rs1398830172
Type: single nucleotide variant
Location: chr5:157241679 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITK p.Ala308Ser Uncertain significance ★★ ⚠ same condition
ITK p.Arg451Trp Uncertain significance ★★ same condition
ITK p.Arg602Trp Uncertain significance ★★ ⚠ same condition
ITK p.Glu196Gln Uncertain significance ★★ ⚠ same condition
ITK p.His378Arg Uncertain significance ★★ ⚠ same condition
ITK p.His586Asp Uncertain significance ★★ ⚠ same condition
ITK p.Ile590Met Uncertain significance ★★ ⚠ same condition
ITK p.Leu612Met 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-phe340ser (accessed [today's date]).

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