Is TYK2 p.Ser570fs (c.1704_1707dup) pathogenic?

TYK2 p.Ser570fs (c.17041707dup) is classified Likely pathogenic in TYK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). Associated with immunodeficiency 35.

What condition is associated with TYK2 p.Ser570fs (c.1704_1707dup)?

TYK2 p.Ser570fs (c.1704_1707dup) is associated with immunodeficiency 35 (ClinVar).

TYK2 p.Ser570fs

Q: How is Susceptibility to infection due to TYK2 deficiency inherited?

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

c.1704_1707dup · VCV4292927

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

immunodeficiency 35

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 12 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.57	GERP -1.6, phastCons 0.27

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

Variant & gene context

Gene: TYK2
Protein: p.Ser570fs
Coding: c.1704_1707dup
MANE Select: NM_003331
Type: Duplication
Location: chr19:10362143 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.69 · 52 PDB

Full TYK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 35 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Susceptibility to infection due to TYK2 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

TYK2 p.Ser570= Likely benign ★ same residue
TYK2 p.Glu636fs Pathogenic/Likely pathogenic ★★ same condition
TYK2 c.1669+16dup Benign/Likely benign ★★ same condition
TYK2 c.3201-11_3201-10dup Likely benign ★★ same condition
TYK2 p.Asn920fs Pathogenic ★ same condition
TYK2 p.Thr1106fs Likely pathogenic ★ same condition
TYK2 p.Thr384fs Pathogenic ★ same condition
TYK2 c.1367+19dup Benign ★ 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/tyk2-p-ser570fs (accessed [today's date]).

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