FLT4 p.Trp838Ter
c.2513G>A · VCV4819656
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
congenital heart defects, multiple types, 7
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 17 of 30 |
| Splicing | ||
| SpliceAI | Δ0.24 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 48.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- FLT4
- Protein
- p.Trp838Ter
- Coding
- c.2513G>A
- MANE Select
- NM_182925
- Type
- single nucleotide variant
- Location
- chr5:180620202 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 2 PDB
- Residue 838
- a UniProt-annotated variant site (in chtd7)
Similar variants
- FLT4 p.Arg318Ter 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
- FLT4 c.1103+18C>T Benign/Likely benign ★★ same condition
- FLT4 c.1103+20A>C Benign/Likely benign ★★ same condition
- FLT4 c.1104-42T>C Benign ★★ 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-trp838ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown