PTPRB p.Ala1027Ser
c.3079G>T · VCV4147649
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0175%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.052 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 66 kb · p 0.021 · regional, not allelic |
| Overall | ||
| CADD | 18.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0175%
European (non-Finnish) · 206/1,179,806 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.0136%
219/1,613,856 alleles · ultra-rare
exomes 197/1,461,524 · genomes 22/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0175% | 5,727 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,927 |
| Admixed American | 0.005% | 20,000 |
| African / African-American | 0.00133% | 75,058 |
| South Asian | 0.0011% | 91,042 |
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.Ala1027Ser
- Coding
- c.3079G>T
- MANE Select
- NM_001109754
- Type
- single nucleotide variant
- Location
- chr12:70571851 (GRCh38)
- Gene constraint
- LOEUF 0.466 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 80.67 · 14 PDB
- Residue 1027
- the fibronectin type-iii 12 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.Ala1088Thr Uncertain significance ★ same type
- PTPRB p.Ala1117Val Uncertain significance ★ same type
- PTPRB p.Ala1305Val 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-ala1027ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown