KDR p.Pro1105Leu
c.3314C>T · VCV4075508
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9936 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9936 | likely pathogenic · top 4% in KDR |
|---|---|---|
| REVEL | 0.877 | moderately pathogenic-leaning |
| SaProt | LLR -9.46 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.8, phastCons 1 |
| Regional constraint | o/e 0.67 | unconstrained · MANE · 2,358 bp · p 5e-06 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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
- KDR
- Protein
- p.Pro1105Leu
- Coding
- c.3314C>T
- MANE Select
- NM_002253
- Type
- single nucleotide variant
- Location
- chr4:55089464 (GRCh38)
- Gene constraint
- LOEUF 0.328 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.67 · 54 PDB
- Residue 1105
- the protein kinase domain; a β-strand
Similar variants
- KDR p.Ala379Val Uncertain significance ★★ ⚠ same type
- KDR p.Ala757Gly Uncertain significance ★★ ⚠ same type
- KDR p.Asp832His Uncertain significance ★★ ⚠ same type
- KDR p.Val416Ala Uncertain significance ★★ ⚠ same type
- KDR p.Ala1030= Benign ★★ same type
- KDR p.Ala532= Benign ★★ same type
- KDR p.Arg842His Likely benign ★★ same type
- KDR p.Cys482Arg Likely benign ★★ ⚠ 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/kdr-p-pro1105leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown