Computational evidence
| Protein change | ||
| AlphaMissense | 0.0869 | likely benign |
|---|---|---|
| REVEL | 0.087 | moderately benign-leaning |
| SaProt | LLR -5.89 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -7.8 | GERP -3 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 9,843 bp · p 0.36 · regional, not allelic |
| Overall | ||
| CADD | 0.017 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Amishnot grpmax-eligible | 0.989% | 101 |
| South Asiangrpmax | 0.121% | 828 |
| European (non-Finnish) | 0.111% | 898 |
| Remaining individualsnot grpmax-eligible | 0.0736% | 1,358 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0541% | 1,849 |
| Admixed American | 0.0517% | 1,935 |
| Middle Eastern | 0.0331% | 3,021 |
| African / African-American | 0.0147% | 6,824 |
| Finnishnot grpmax-eligible | 0.0141% | 7,105 |
Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg1324Pro
- Coding
- c.3971G>C
- MANE Select
- NM_182925
- dbSNP
- rs307821
- Type
- single nucleotide variant
- Location
- chr5:180603313 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 2 PDB
- Residue 1324
- the 'disordered' region; a UniProt-annotated variant site (in chtd7)
Similar variants
- FLT4 p.Arg1324Leu Benign ★★ 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-arg1324pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown