FLRT3 p.Leu441=
c.1323T>C · rs143784361 · VCV735414
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.235%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.7 | GERP 0.18, phastCons 1 |
| Overall | ||
| CADD | 8.666 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.235%
Admixed American · 141/59,988 alleles
Filtering AF
0.203%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.191%
Overall
0.0149%
240/1,613,914 alleles · rare
exomes 215/1,461,640 · genomes 25/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.235% | 425 |
| Middle Eastern | 0.0495% | 2,019 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,840 |
| African / African-American | 0.0133% | 7,501 |
| European (non-Finnish) | 0.00534% | 18,728 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,590 |
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
- FLRT3
- Protein
- p.Leu441=
- Coding
- c.1323T>C
- MANE Select
- NM_198391
- dbSNP
- rs143784361
- Type
- single nucleotide variant
- Location
- chr20:14326184 (GRCh38)
- Gene constraint
- LOEUF 0.585 · pLI 0.55 (gnomAD)
- Structure
- AlphaFold pLDDT 74.57 · 3 PDB
- Residue 441
- the fibronectin type-iii domain
Similar variants
- FLRT3 p.Arg163Cys Uncertain significance ★★ ⚠ same type
- FLRT3 p.Leu109Val Uncertain significance ★★ ⚠ same type
- FLRT3 p.Ser25Pro Uncertain significance ★★ ⚠ same type
- FLRT3 p.Ser284Arg Uncertain significance ★★ ⚠ same type
- FLRT3 p.Ser33Pro Uncertain significance ★★ ⚠ same type
- FLRT3 p.Thr199Ser Uncertain significance ★★ ⚠ same type
- FLRT3 p.Thr419Ser Uncertain significance ★★ ⚠ same type
- FLRT3 p.Trp381Arg 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/flrt3-p-leu441 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown