F11 p.Leu589=
c.1767G>T · rs142054643 · VCV989876
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0707%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.103 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.26 | acceptor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 5.7 | GERP 2.4, phastCons 1 |
| Overall | ||
| CADD | 15.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0707%
African / African-American · 53/74,926 alleles
Filtering AF
0.0555%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0501%
Overall
0.00446%
72/1,614,068 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0707% | 1,414 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,207 |
| Middle Eastern | 0.0164% | 6,084 |
| Admixed American | 0.01% | 10,001 |
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
- F11
- Protein
- p.Leu589=
- Coding
- c.1767G>T
- MANE Select
- NM_001322131 · reported on NM_000128
- dbSNP
- rs142054643
- Type
- single nucleotide variant
- Location
- chr4:186288503 (GRCh38)
- Structure
- AlphaFold pLDDT 68.98
Similar variants
- F11 p.Leu589Pro Uncertain significance ⚠ same residue
- F11 c.1136-1G>C Likely pathogenic ★★ same type
- F11 c.1480+1G>T Likely pathogenic ★★ same type
- F11 c.1481-1G>T Likely pathogenic ★★ same type
- F11 c.1716+1G>A Pathogenic ★★ same type
- F11 c.325+1G>A Pathogenic ★★ same type
- F11 c.326-1G>A Pathogenic ★★ same type
- F11 c.595+3A>G Pathogenic/Likely pathogenic ★★ 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/f11-p-leu589 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown