Is TYK2 p.Gln855Arg (c.2564A>G) pathogenic?

TYK2 p.Gln855Arg (c.2564A>G) is classified Uncertain significance in TYK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: likely benign (0.0726); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TYK2 p.Gln855Arg (c.2564A>G)?

TYK2 p.Gln855Arg (c.2564A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TYK2 p.Gln855Arg (c.2564A>G) in the general population?

TYK2 p.Gln855Arg (c.2564A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TYK2 p.Gln855Arg (c.2564A>G)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

TYK2 p.Gln855Arg

c.2564A>G · rs2512486232 · VCV2310198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.425	indeterminate
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.89, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 6.7e-09 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Gln855Arg
Coding: c.2564A>G
MANE Select: NM_003331
dbSNP: rs2512486232
Type: single nucleotide variant
Location: chr19:10356621 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.69 · 52 PDB
Residue 855: an α-helix; the protein kinase 1 domain

Full TYK2 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

TYK2 p.Ala1026Thr Uncertain significance ★★ ⚠ same condition
TYK2 p.Ala428Thr Uncertain significance ★★ ⚠ same condition
TYK2 p.Ala567Thr Uncertain significance ★★ ⚠ same condition
TYK2 p.Ala671Thr Uncertain significance ★★ ⚠ same condition
TYK2 p.Arg269His Uncertain significance ★★ ⚠ same condition
TYK2 p.Arg274Cys Uncertain significance ★★ ⚠ same condition
TYK2 p.Arg294Trp Uncertain significance ★★ ⚠ same condition
TYK2 p.Arg410Trp 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-gln855arg (accessed [today's date]).

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