FLT4 p.Glu246fs
c.736dup · VCV4888339
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
congenital heart defects, multiple types, 7
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 30 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 1.6, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- FLT4
- Protein
- p.Glu246fs
- Coding
- c.736dup
- MANE Select
- NM_182925
- Type
- Duplication
- Location
- chr5:180629775 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 2 PDB
- Residue 246
- a UniProt-annotated variant site (in chtd7); the ig-like c2-type 3 domain
Similar variants
- FLT4 p.Glu570fs Pathogenic ★ same condition
- FLT4 p.Gln542fs Pathogenic same condition
- FLT4 p.Arg318Ter Pathogenic/Likely pathogenic ★★ same condition
- FLT4 p.Glu100fs Pathogenic/Likely pathogenic ★★ same condition
- FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
- FLT4 p.Arg1060Gln Uncertain significance ★★ ⚠ same condition
- FLT4 p.Met1260Leu Uncertain significance ★★ ⚠ same condition
- FLT4 p.Pro922Leu Uncertain significance ★★ ⚠ 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-glu246fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown