FLT4 p.Ala491=
c.1473G>A · rs181584754 · VCV755441
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.12%, eas)
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 -0.92 | GERP -1.1, phastCons 0.002 |
| Overall | ||
| CADD | 7.725 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.12%
East Asian · 54/44,880 alleles
Filtering AF
0.0946%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0855%
Overall
0.00452%
73/1,613,410 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.12% | 831 |
| South Asian | 0.00549% | 18,217 |
| African / African-American | 0.00533% | 18,760 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,832 |
| Admixed American | 0.00167% | 60,022 |
| Finnishnot grpmax-eligible | 0.00158% | 63,318 |
| European (non-Finnish) | 0.000424% | 235,998 |
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.Ala491=
- Coding
- c.1473G>A
- MANE Select
- NM_182925
- dbSNP
- rs181584754
- Type
- single nucleotide variant
- Location
- chr5:180624010 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 2 PDB
- Residue 491
- a disulfide bond; a UniProt-annotated variant site (in chtd7); the ig-like c2-type 5 domain
Similar variants
- FLT4 p.Ala491Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- FLT4 p.Arg1041Gln Pathogenic/Likely pathogenic ★★ same type
- FLT4 p.Arg1041Trp Pathogenic/Likely pathogenic ★★ same type
- FLT4 p.Arg318Ter Pathogenic/Likely pathogenic ★★ same type
- FLT4 p.Gly1131Ser Pathogenic/Likely pathogenic ★★ same type
- FLT4 p.Gly857Arg Pathogenic ★★ same type
- FLT4 p.Pro1137Leu Likely pathogenic ★★ same type
- FLT4 p.Ala702Ser Uncertain significance ★★ ⚠ 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/flt4-p-ala491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown