PTPN6 p.Pro399=
c.1197G>A · rs116298095 · VCV778582
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.65%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.6 | GERP -3.3 |
| Overall | ||
| CADD | 0.424 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.65%
African / African-American · 2,738/75,042 alleles
Filtering AF
3.53%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.49%
Overall
0.251%
4,057/1,614,124 alleles · low-frequency
exomes 2,262/1,461,792 · genomes 1,795/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.65% | 27 |
| Ashkenazi Jewishnot grpmax-eligible | 1.67% | 60 |
| Remaining individualsnot grpmax-eligible | 0.434% | 231 |
| Admixed American | 0.387% | 259 |
| Middle Eastern | 0.313% | 319 |
| European (non-Finnish) | 0.0249% | 4,014 |
| South Asian | 0.00878% | 11,386 |
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
- PTPN6
- Protein
- p.Pro399=
- Coding
- c.1197G>A
- MANE Select
- NM_002831
- dbSNP
- rs116298095
- Type
- single nucleotide variant
- Location
- chr12:6957776 (GRCh38)
- Gene constraint
- LOEUF 0.325 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.54 · 14 PDB
- Residue 399
- the tyrosine-protein phosphatase domain; a β-strand
Similar variants
- PTPN6 c.9-7C>T Uncertain significance ★★ same type
- PTPN6 p.Cys361= Benign ★★ same type
- PTPN6 p.Ser42= Benign ★★ same type
- PTPN6 c.1206+2T>G Uncertain significance ★ same type
- PTPN6 c.1674-22G>C Uncertain significance ★ same type
- PTPN6 c.1674-34C>G Uncertain significance ★ same type
- PTPN6 c.1674-42T>C Uncertain significance ★ same type
- PTPN6 c.1674-51C>G 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/ptpn6-p-pro399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown