PTPRB p.Val63Ile
c.187G>A · VCV3940657
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0396%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.006 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -4.5 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 66 kb · p 0.021 · regional, not allelic |
| Overall | ||
| CADD | 1.217 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0396%
South Asian · 36/91,018 alleles
Filtering AF
0.0293%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0258%
Overall
0.00229%
37/1,613,694 alleles · ultra-rare
exomes 36/1,461,430 · genomes 1/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0396% | 2,528 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
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
- PTPRB
- Protein
- p.Val63Ile
- Coding
- c.187G>A
- MANE Select
- NM_001109754
- Type
- single nucleotide variant
- Location
- chr12:70635935 (GRCh38)
- Gene constraint
- LOEUF 0.466 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 80.67 · 14 PDB
- Residue 63
- the fibronectin type-iii 1 domain
Similar variants
- PTPRB c.3370+4A>G Benign ★★ same type
- PTPRB p.Ala1520= Benign ★★ same type
- PTPRB p.Leu1142= Benign ★★ same type
- PTPRB p.Pro1816= Benign/Likely benign ★★ same type
- PTPRB p.Thr1699= Benign ★★ same type
- PTPRB p.Ala1027Ser Uncertain significance ★ same type
- PTPRB p.Ala1088Thr Uncertain significance ★ same type
- PTPRB p.Ala1117Val 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/ptprb-p-val63ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown