FLT4 p.Arg745=
c.2235C>G · rs199935385 · VCV3054395
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.246%, amr)
Conditions
1
FLT4-related disorder
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 1.5 | GERP -2.2, phastCons 0.99 |
| Overall | ||
| CADD | 11.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.246%
Admixed American · 147/59,750 alleles
Filtering AF
0.214%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.201%
Overall
0.00925%
149/1,610,552 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.246% | 406 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,186 |
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
- FLT4
- Protein
- p.Arg745=
- Coding
- c.2235C>G
- MANE Select
- NM_182925
- dbSNP
- rs199935385
- Type
- single nucleotide variant
- Location
- chr5:180620940 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 2 PDB
- Residue 745
- the ig-like c2-type 7 domain; a disulfide bond; a UniProt-annotated variant site (in chtd7)
Disease context
FLT4-related disorder
Similar variants
- FLT4 p.Gly857Arg Pathogenic ★★ same condition
- FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
- FLT4 p.Ser393Arg Uncertain significance ★★ ⚠ same condition
- FLT4 c.2168-1G>A Likely pathogenic ★ same condition
- FLT4 p.Arg1041Gly Likely pathogenic ★ same condition
- FLT4 p.Gln1020Leu Pathogenic ★ same condition
- FLT4 p.Gln1179Ter Pathogenic ★ same condition
- FLT4 p.Gly1276Glu 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/flt4-p-arg745 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown