LEFTY2 p.Ala86=
c.258C>T · rs777331120 · VCV706399
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 -5.4 | GERP -2.9 |
| Overall | ||
| CADD | 12.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,860 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00083%
Overall
0.00138%
22/1,595,690 alleles · very rare
exomes 15/1,443,440 · genomes 7/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,430 |
| Admixed American | 0.00167% | 59,980 |
| European (non-Finnish) | 0.00161% | 62,084 |
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
- LEFTY2
- Protein
- p.Ala86=
- Coding
- c.258C>T
- MANE Select
- NM_003240
- dbSNP
- rs777331120
- Type
- single nucleotide variant
- Location
- chr1:225939995 (GRCh38)
- Gene constraint
- LOEUF 0.703 · pLI 0.35 (gnomAD)
- Structure
- AlphaFold pLDDT 79.01
Similar variants
- LEFTY2 p.Arg243Gly Uncertain significance ★★ ⚠ same type
- LEFTY2 p.Arg265Cys Uncertain significance ★★ ⚠ same type
- LEFTY2 p.Arg314Gln Uncertain significance ★★ ⚠ same type
- LEFTY2 p.Arg33Trp Uncertain significance ★★ ⚠ same type
- LEFTY2 p.Arg67His Uncertain significance ★★ ⚠ same type
- LEFTY2 p.Arg83Gly Uncertain significance ★★ ⚠ same type
- LEFTY2 p.Asp241Glu Uncertain significance ★★ same type
- LEFTY2 p.Asp356Asn 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/lefty2-p-ala86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown