LRRC8A p.Thr282=
c.846C>T · rs534343827 · VCV1653385
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0446%, eas)
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 -13 | GERP -4 |
| Overall | ||
| CADD | 1.204 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0446%
East Asian · 20/44,884 alleles
Filtering AF
0.0295%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0246%
Overall
0.00545%
88/1,613,964 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0446% | 2,244 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| European (non-Finnish) | 0.00458% | 21,853 |
| South Asian | 0.00439% | 22,769 |
| African / African-American | 0.00401% | 24,962 |
| Admixed American | 0.00333% | 29,996 |
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.Thr282=
- Coding
- c.846C>T
- MANE Select
- NM_019594
- dbSNP
- rs534343827
- Type
- single nucleotide variant
- Location
- chr9:128908010 (GRCh38)
- Gene constraint
- LOEUF 0.614 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 85.52 · 13 PDB
- Residue 282
- an α-helix
Similar variants
- LRRC8A p.Thr282Ala Uncertain significance ★ ⚠ same residue
- 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
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-thr282 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown