LEFTY2 p.Asp164=
c.492C>T · rs780037300 · VCV3031603
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0105%, amr)
Conditions
1
LEFTY2-related disorder
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 2.2 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 13.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0105%
Admixed American · 6/56,996 alleles
Filtering AF
0.00457%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00308%
Overall
0.000376%
6/1,594,456 alleles · ultra-rare
exomes 6/1,442,092 · genomes 0/152,364 · joint denominator
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.Asp164=
- Coding
- c.492C>T
- MANE Select
- NM_003240
- dbSNP
- rs780037300
- Type
- single nucleotide variant
- Location
- chr1:225939761 (GRCh38)
- Gene constraint
- LOEUF 0.703 · pLI 0.35 (gnomAD)
- Structure
- AlphaFold pLDDT 79.01
Disease context
LEFTY2-related disorder
Similar variants
- LEFTY2 p.Arg83Gly Uncertain significance ★★ ⚠ same condition
- LEFTY2 p.Val40Leu Uncertain significance ★★ ⚠ same condition
- 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.Asp241Glu 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-asp164 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown