PTPRB p.Ser1973Phe
c.5918C>T · VCV4147689
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.653 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.79 | unconstrained · MANE · 23 kb · p 2.8e-06 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,982 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000248%
4/1,613,718 alleles · very rare
exomes 3/1,461,494 · genomes 1/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,994 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
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.Ser1973Phe
- Coding
- c.5918C>T
- MANE Select
- NM_001109754
- Type
- single nucleotide variant
- Location
- chr12:70538183 (GRCh38)
- Gene constraint
- LOEUF 0.466 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 80.67 · 14 PDB
Similar variants
- PTPRB p.Ser1973Pro Uncertain significance ★ same residue
- 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
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-ser1973phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown