Is TYK2 p.Ser171= (c.513G>A) pathogenic?

TYK2 p.Ser171= (c.513G>A) is classified Benign/Likely benign in TYK2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-10). Rare (popmax 0.517%, eas); Associated with immunodeficiency 35.

What condition is associated with TYK2 p.Ser171= (c.513G>A)?

TYK2 p.Ser171= (c.513G>A) is associated with immunodeficiency 35 (ClinVar).

How common is TYK2 p.Ser171= (c.513G>A) in the general population?

TYK2 p.Ser171= (c.513G>A) is rare (popmax 0.517%, eas) (gnomAD).

TYK2 p.Ser171=

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.513G>A · rs55988893 · VCV327959

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.517%, eas)

Conditions

immunodeficiency 35

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.6
Overall
CADD	0.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.517% East Asian · 232/44,874 alleles

Filtering AF 0.462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.441%

Overall 0.0281% 453/1,613,952 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.517%	193
Remaining individualsnot grpmax-eligible	0.243%	411
Admixed American	0.0667%	1,499
African / African-American	0.00267%	37,489
European (non-Finnish)	0.0022%	45,384
South Asian	0.0011%	91,066

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: TYK2
Protein: p.Ser171=
Coding: c.513G>A
MANE Select: NM_003331
dbSNP: rs55988893
Type: single nucleotide variant
Location: chr19:10366533 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.69 · 52 PDB
Residue 171: the ferm domain

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.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
TYK2 p.Ala413Val 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-ser171 (accessed [today's date]).

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