LEFTY2 p.Pro286=
c.858G>A · rs772445393 · VCV1111805
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
Conditions
1
Left-right axis malformations
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 -14 | GERP -3.6 |
| Overall | ||
| CADD | 1.591 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/59,996 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00186%
30/1,613,782 alleles · ultra-rare
exomes 28/1,461,570 · genomes 2/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,615 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| South Asian | 0.00329% | 30,359 |
| East Asian | 0.00223% | 44,874 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,464 |
| European (non-Finnish) | 0.000932% | 107,257 |
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.Pro286=
- Coding
- c.858G>A
- MANE Select
- NM_003240
- dbSNP
- rs772445393
- Type
- single nucleotide variant
- Location
- chr1:225937684 (GRCh38)
- Gene constraint
- LOEUF 0.703 · pLI 0.35 (gnomAD)
- Structure
- AlphaFold pLDDT 79.01
- Residue 286
- a UniProt-annotated variant site (in)
Similar variants
- LEFTY2 p.Pro286Leu Benign/Likely benign ★★ same residue
- LEFTY2 p.Arg243Gly Uncertain significance ★★ ⚠ same condition
- LEFTY2 p.Arg265Cys Uncertain significance ★★ ⚠ same condition
- LEFTY2 p.Arg314Gln Uncertain significance ★★ ⚠ same condition
- LEFTY2 p.Arg33Trp Uncertain significance ★★ ⚠ same condition
- LEFTY2 p.Arg67His Uncertain significance ★★ ⚠ same condition
- LEFTY2 p.Asp241Glu Uncertain significance ★★ same condition
- LEFTY2 p.Asp356Asn Uncertain significance ★★ ⚠ same condition
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-pro286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown