TYK2 p.Pro216=
c.648G>A · rs142642403 · VCV788263
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0545%, nfe)
Conditions
3
Recurrent skin infections
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 -13 | GERP -3.9 |
| Overall | ||
| CADD | 1.846 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0545%
European (non-Finnish) · 642/1,178,818 alleles
Filtering AF
0.051%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0496%
Overall
0.044%
708/1,610,626 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0545% | 1,836 |
| Remaining individualsnot grpmax-eligible | 0.0321% | 3,118 |
| South Asian | 0.0287% | 3,489 |
| Middle Eastern | 0.0166% | 6,042 |
| Admixed American | 0.0151% | 6,634 |
| African / African-American | 0.008% | 12,501 |
| East Asian | 0.00446% | 22,404 |
| Finnishnot grpmax-eligible | 0.00319% | 31,393 |
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.Pro216=
- Coding
- c.648G>A
- MANE Select
- NM_003331
- dbSNP
- rs142642403
- Type
- single nucleotide variant
- Location
- chr19:10365880 (GRCh38)
- Gene constraint
- LOEUF 0.626 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.69 · 52 PDB
- Residue 216
- the ferm domain
Similar variants
- TYK2 p.Pro216Leu Uncertain significance ★ ⚠ same residue
- TYK2 p.Pro216fs Pathogenic/Likely pathogenic ★★ 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
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-pro216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown