PTPN11 p.Lys124=
c.372A>G · rs1035774225 · VCV514728
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Cardiovascular phenotype
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 0.89 | GERP 0.36, phastCons 0.89 |
| Overall | ||
| CADD | 8.642 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PTPN11
- Protein
- p.Lys124=
- Coding
- c.372A>G
- MANE Select
- NM_002834
- dbSNP
- rs1035774225
- Type
- single nucleotide variant
- Location
- chr12:112453234 (GRCh38)
- Gene constraint
- LOEUF 0.156 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 86.34 · 117 PDB
- Residue 124
- an α-helix; the sh2 2 domain
Similar variants
- PTPN11 p.Ala72Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PTPN11 p.Arg231Ter Pathogenic/Likely pathogenic ★★ same condition
- PTPN11 p.Arg265Leu Likely pathogenic ★★ same condition
- PTPN11 p.Asp61His Pathogenic ★★ same condition
- PTPN11 p.Gln256Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PTPN11 p.Glu110Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PTPN11 p.Gly60Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PTPN11 p.Ile282Met Pathogenic/Likely pathogenic ★★ same condition
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/ptpn11-p-lys124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown