Is TYK2 p.Asp78Tyr (c.232G>T) pathogenic?

TYK2 p.Asp78Tyr (c.232G>T) is classified Uncertain significance in TYK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-21). AlphaMissense: ambiguous (0.3593); Absent from gnomAD v4.1; Associated with immunodeficiency 35.

What condition is associated with TYK2 p.Asp78Tyr (c.232G>T)?

TYK2 p.Asp78Tyr (c.232G>T) is associated with immunodeficiency 35 (ClinVar).

How common is TYK2 p.Asp78Tyr (c.232G>T) in the general population?

TYK2 p.Asp78Tyr (c.232G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TYK2 p.Asp78Tyr (c.232G>T)?

AlphaMissense predicts ambiguous (score 0.3593) — an in-silico prediction, not a clinical call.

TYK2 p.Asp78Tyr

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.232G>T · rs778171865 · VCV940796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3593 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

immunodeficiency 35

Computational evidence

Protein change
AlphaMissense	0.3593	ambiguous
REVEL	0.408	indeterminate
SaProt	LLR -13.37	damaging
Splicing
SpliceAI	Δ0.29	acceptor gain · deltas
Pangolin	Δ0.35	loss · gain 0.16 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 1.3	GERP 0.7, phastCons 0.71
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 6.7e-09 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TYK2
Protein: p.Asp78Tyr
Coding: c.232G>T
MANE Select: NM_003331
dbSNP: rs778171865
Type: single nucleotide variant
Location: chr19:10368380 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.69 · 52 PDB
Residue 78: the ferm domain; a β-strand

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.Asp78Asn Uncertain significance ★ ⚠ same residue
TYK2 p.Arg609Ter Pathogenic/Likely pathogenic ★★ same condition
TYK2 p.Trp798Ter Pathogenic ★★ same condition
TYK2 p.Ala1004Gly Uncertain significance ★★ ⚠ same condition
TYK2 p.Ala1026Thr Uncertain significance ★★ ⚠ same condition
TYK2 p.Ala165Thr Uncertain significance ★★ ⚠ same condition
TYK2 p.Ala195Ser Uncertain significance ★★ ⚠ same condition
TYK2 p.Ala195Thr 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/tyk2-p-asp78tyr (accessed [today's date]).

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