PTPN2 p.Ser166=
c.498T>C · VCV4872846
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.354%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.25 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 0.63, phastCons 1 |
| Overall | ||
| CADD | 12.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.354%
African / African-American · 265/74,888 alleles
Filtering AF
0.319%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.305%
Overall
0.0184%
296/1,611,076 alleles · rare
exomes 169/1,458,838 · genomes 127/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.354% | 283 |
| Middle Eastern | 0.033% | 3,026 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,456 |
| Admixed American | 0.0184% | 5,424 |
| South Asian | 0.00221% | 45,340 |
| European (non-Finnish) | 0.00017% | 589,043 |
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
- PTPN2
- Protein
- p.Ser166=
- Coding
- c.498T>C
- MANE Select
- NM_002828
- Type
- single nucleotide variant
- Location
- chr18:12817363 (GRCh38)
- Gene constraint
- LOEUF 0.618 · pLI 0.51 (gnomAD)
- Structure
- AlphaFold pLDDT 86.20 · 14 PDB
- Residue 166
- the tyrosine-protein phosphatase domain; a turn
Similar variants
- PTPN2 p.Thr171Lys Benign ★★ same type
- PTPN2 p.Val234Ile Benign ★★ same type
- PTPN2 p.Arg45Ter Likely pathogenic ★ same type
- PTPN2 c.161-3856C>T Uncertain significance ★ same type
- PTPN2 c.360+1G>C Uncertain significance ★ same type
- PTPN2 p.Ala212Val Uncertain significance ★ ⚠ same type
- PTPN2 p.Ala276Thr Uncertain significance ★ ⚠ same type
- PTPN2 p.Arg16Leu Uncertain significance ★ ⚠ same type
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/ptpn2-p-ser166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown