PTPN3 p.Pro178=
c.534C>T · rs770220726 · VCV2659409
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -0.41 | GERP -4.7, phastCons 0.065 |
| Overall | ||
| CADD | 6.075 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000868%
14/1,613,628 alleles · ultra-rare
exomes 12/1,461,512 · genomes 2/152,116 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.00333% | 29,994 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| East Asian | 0.00223% | 44,886 |
| African / African-American | 0.00134% | 74,882 |
| South Asian | 0.0011% | 91,044 |
| European (non-Finnish) | 0.000509% | 196,622 |
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.Pro178=
- Coding
- c.534C>T
- MANE Select
- NM_002829
- dbSNP
- rs770220726
- Type
- single nucleotide variant
- Location
- chr9:109438167 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.85 · 13 PDB
- Residue 178
- the ferm domain
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-pro178 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown