LRRC8A p.Phe390=
c.1170C>T · rs139427858 · VCV1915753
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, 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 -10 | GERP -4 |
| Overall | ||
| CADD | 1.894 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
East Asian · 9/44,900 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00779%
Overall
0.00328%
53/1,614,006 alleles · ultra-rare
exomes 50/1,461,784 · genomes 3/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.02% | 4,989 |
| Middle Eastern | 0.0164% | 6,084 |
| Admixed American | 0.005% | 20,003 |
| South Asian | 0.00439% | 22,773 |
| European (non-Finnish) | 0.00297% | 33,716 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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.Phe390=
- Coding
- c.1170C>T
- MANE Select
- NM_019594
- dbSNP
- rs139427858
- Type
- single nucleotide variant
- Location
- chr9:128908334 (GRCh38)
- Gene constraint
- LOEUF 0.614 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 85.52 · 13 PDB
- Residue 390
- an α-helix
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-phe390 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown