PTPN3 p.Pro616=
c.1848C>T · VCV3427877
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00865%, amr)
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 -1 | GERP -4.1, phastCons 0.003 |
| Overall | ||
| CADD | 5.568 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00865%
Admixed American · 5/57,774 alleles
Filtering AF
0.00336%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00213%
Overall
0.000638%
10/1,566,862 alleles · very rare
exomes 9/1,414,690 · genomes 1/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00865% | 11,555 |
| East Asian | 0.00228% | 43,920 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,458 |
| African / African-American | 0.00134% | 74,466 |
| South Asian | 0.00122% | 81,882 |
| European (non-Finnish) | 8.7e-05% | 1,149,366 |
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
- PTPN3
- Protein
- p.Pro616=
- Coding
- c.1848C>T
- MANE Select
- NM_002829
- Type
- single nucleotide variant
- Location
- chr9:109404553 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.85 · 13 PDB
Similar variants
- PTPN3 p.Asn612Thr Uncertain significance ★★ ⚠ same type
- PTPN3 p.Ile715= Benign ★★ same type
- PTPN3 p.Ala146Thr Uncertain significance ★ ⚠ same type
- PTPN3 p.Ala150Val Uncertain significance ★ ⚠ same type
- PTPN3 p.Ala153Val Uncertain significance ★ ⚠ same type
- PTPN3 p.Ala310Pro Uncertain significance ★ same type
- PTPN3 p.Ala400Glu Uncertain significance ★ ⚠ same type
- PTPN3 p.Arg16Cys 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/ptpn3-p-pro616 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown