Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 35.3%, mid) — too common for a highly-penetrant pathogenic allele
Conditions
2
congenital heart defects, multiple types, 7
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 -4.3 | GERP -3.5 |
| Overall | ||
| CADD | 3.621 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
35.3%
Middle Eastern · 2,140/6,062 alleles
Filtering AF
34.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 34.2%
Overall
27.4%
442,788/1,613,624 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 35.3% | 3 |
| South Asian | 34.6% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 31.4% | 3 |
| European (non-Finnish) | 28.2% | 4 |
| Remaining individualsnot grpmax-eligible | 28% | 4 |
| Amishnot grpmax-eligible | 25.1% | 4 |
| East Asian | 25% | 4 |
| Finnishnot grpmax-eligible | 23% | 4 |
| Admixed American | 18.9% | 5 |
| African / African-American | 17% | 6 |
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.Pro1066=
- Coding
- c.3198C>T
- MANE Select
- NM_182925
- dbSNP
- rs1130378
- Type
- single nucleotide variant
- Location
- chr5:180616388 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 2 PDB
- Residue 1066
- the protein kinase domain; a UniProt-annotated variant site (in chtd7)
Similar variants
- FLT4 p.Arg1041Gln Pathogenic/Likely pathogenic ★★ same condition
- FLT4 p.Arg1041Trp Pathogenic/Likely pathogenic ★★ same condition
- FLT4 p.Arg318Ter Pathogenic/Likely pathogenic ★★ same condition
- FLT4 p.Gly857Arg Pathogenic ★★ same condition
- FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
- FLT4 p.Ala702Ser Uncertain significance ★★ ⚠ same condition
- FLT4 p.Ala855Thr Uncertain significance ★★ ⚠ same condition
- FLT4 p.Arg1060Gln 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-pro1066 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown