PTPRO p.His438=
c.1314C>T · rs140514339 · VCV2959395
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00669%, eas)
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 · C>G here scores Δ0.52 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -5.9 |
| Overall | ||
| CADD | 0.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00669%
East Asian · 3/44,844 alleles
Filtering AF
0.00426%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00387%
Overall
0.00452%
73/1,614,042 alleles · very rare
exomes 66/1,461,804 · genomes 7/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00669% | 14,948 |
| European (non-Finnish) | 0.00534% | 18,730 |
| African / African-American | 0.00533% | 18,755 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
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
- PTPRO
- Protein
- p.His438=
- Coding
- c.1314C>T
- MANE Select
- NM_030667
- dbSNP
- rs140514339
- Type
- single nucleotide variant
- Location
- chr12:15508617 (GRCh38)
- Gene constraint
- LOEUF 0.513 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 77.55 · 2 PDB
- Residue 438
- the fibronectin type-iii 5 domain
Similar variants
- PTPRO p.Ala1086Val Uncertain significance ★★ ⚠ same type
- PTPRO p.Ala591Thr Uncertain significance ★★ ⚠ same type
- PTPRO p.Arg480Trp Uncertain significance ★★ same type
- PTPRO p.Arg607Gln Uncertain significance ★★ ⚠ same type
- PTPRO p.Asn569Asp Uncertain significance ★★ ⚠ same type
- PTPRO p.Asp162Val Uncertain significance ★★ ⚠ same type
- PTPRO p.Asp301His Uncertain significance ★★ ⚠ same type
- PTPRO p.Asp799Gly 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/ptpro-p-his438 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown