LRRC8A p.Leu596=
c.1788G>A · rs116679304 · VCV716198
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.29%, 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 2.1 | GERP -0.24, phastCons 1 |
| Overall | ||
| CADD | 4.469 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.29%
African / African-American · 971/75,024 alleles
Filtering AF
1.23%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.2%
Overall
0.0651%
1,050/1,614,132 alleles · low-frequency
exomes 545/1,461,842 · genomes 505/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.29% | 77 |
| Middle Eastern | 0.0825% | 1,212 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,563 |
| Admixed American | 0.0433% | 2,309 |
| South Asian | 0.00439% | 22,773 |
| European (non-Finnish) | 0.000339% | 295,009 |
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
- LRRC8A
- Protein
- p.Leu596=
- Coding
- c.1788G>A
- MANE Select
- NM_019594
- dbSNP
- rs116679304
- Type
- single nucleotide variant
- Location
- chr9:128908952 (GRCh38)
- Gene constraint
- LOEUF 0.614 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 85.52 · 13 PDB
- Residue 596
- a β-strand
Similar variants
- LRRC8A p.Ala497Val Uncertain significance ★★ ⚠ same type
- LRRC8A p.Arg148His Uncertain significance ★★ ⚠ same type
- LRRC8A p.Arg214Gln Uncertain significance ★★ ⚠ same type
- LRRC8A p.Arg218Gln Uncertain significance ★★ ⚠ same type
- LRRC8A p.Arg218Trp Uncertain significance ★★ ⚠ same type
- LRRC8A p.Arg262Cys Uncertain significance ★★ ⚠ same type
- LRRC8A p.Arg496Gln Uncertain significance ★★ ⚠ same type
- LRRC8A p.Arg545Cys 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/lrrc8a-p-leu596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown