LEF1 p.Ser109=
c.327G>A · rs61751709 · VCV783383
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.75%, afr)
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 -5.5 | GERP -5.7 |
| Overall | ||
| CADD | 4.76 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.75%
African / African-American · 1,312/75,002 alleles
Filtering AF
1.67%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.64%
Overall
0.118%
1,906/1,613,780 alleles · low-frequency
exomes 1,147/1,461,572 · genomes 759/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.75% | 57 |
| Ashkenazi Jewishnot grpmax-eligible | 0.439% | 228 |
| Admixed American | 0.22% | 455 |
| Remaining individualsnot grpmax-eligible | 0.152% | 658 |
| Middle Eastern | 0.149% | 673 |
| European (non-Finnish) | 0.0189% | 5,291 |
| South Asian | 0.00549% | 18,208 |
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
- LEF1
- Protein
- p.Ser109=
- Coding
- c.327G>A
- MANE Select
- NM_016269
- dbSNP
- rs61751709
- Type
- single nucleotide variant
- Location
- chr4:108163655 (GRCh38)
- Gene constraint
- LOEUF 0.459 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 57.74
Similar variants
- LEF1 p.Asp85Asn Benign/Likely benign ★★ same type
- LEF1 p.Ala305Thr Uncertain significance ★ ⚠ same type
- LEF1 p.Ala352Thr Uncertain significance ★ ⚠ same type
- LEF1 p.Arg296Lys Uncertain significance ★ ⚠ same type
- LEF1 p.Asn59Lys Uncertain significance ★ ⚠ same type
- LEF1 p.Asp177Val Uncertain significance ★ ⚠ same type
- LEF1 p.Asp276Asn Uncertain significance ★ ⚠ same type
- LEF1 p.Asp31Glu 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/lef1-p-ser109 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown