KDR p.His546=
c.1638C>T · rs141120216 · VCV697105
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.233%, 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 -9.5 | GERP -5.2 |
| Overall | ||
| CADD | 0.432 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.233%
African / African-American · 174/74,634 alleles
Filtering AF
0.205%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.194%
Overall
0.0121%
193/1,597,434 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.233% | 429 |
| Remaining individualsnot grpmax-eligible | 0.0161% | 6,198 |
| Admixed American | 0.005% | 19,995 |
| East Asian | 0.00223% | 44,806 |
| Finnishnot grpmax-eligible | 0.00156% | 64,030 |
| South Asian | 0.0011% | 90,756 |
| European (non-Finnish) | 0.000258% | 388,270 |
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
- KDR
- Protein
- p.His546=
- Coding
- c.1638C>T
- MANE Select
- NM_002253
- dbSNP
- rs141120216
- Type
- single nucleotide variant
- Location
- chr4:55105839 (GRCh38)
- Gene constraint
- LOEUF 0.328 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.67 · 54 PDB
- Residue 546
- a β-strand; the ig-like c2-type 5 domain
Similar variants
- KDR p.His546Pro Uncertain significance ★ ⚠ same residue
- 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
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-his546 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown