PTPRO p.Val377=
c.1131G>A · rs368790873 · VCV2885429
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00674%, afr)
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 2.3 | GERP 0.23, phastCons 1 |
| Overall | ||
| CADD | 4.955 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00674%
African / African-American · 5/74,142 alleles
Filtering AF
0.00257%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00163%
Overall
0.000505%
8/1,583,424 alleles · very rare
exomes 3/1,431,340 · genomes 5/152,084 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00674% | 14,828 |
| Remaining individualsnot grpmax-eligible | 0.00325% | 30,733 |
| Admixed American | 0.00167% | 59,914 |
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.Val377=
- Coding
- c.1131G>A
- MANE Select
- NM_030667
- dbSNP
- rs368790873
- Type
- single nucleotide variant
- Location
- chr12:15503933 (GRCh38)
- Gene constraint
- LOEUF 0.513 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 77.55 · 2 PDB
- Residue 377
- the fibronectin type-iii 4 domain
Similar variants
- PTPRO p.Val377Met Uncertain significance ★ ⚠ same residue
- 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
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-val377 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown