LRRC8A p.Ala111=
c.333T>C · rs16930747 · VCV1164444
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 8.43%, afr) — too common for a highly-penetrant pathogenic allele
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 -15 | GERP -4 |
| Overall | ||
| CADD | 0.135 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.43%
African / African-American · 6,322/75,016 alleles
Filtering AF
8.25%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.18%
Overall
1.17%
18,822/1,614,064 alleles · common
exomes 14,357/1,461,790 · genomes 4,465/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.43% | 12 |
| East Asian | 7.17% | 14 |
| South Asian | 3.25% | 31 |
| Admixed American | 1.62% | 62 |
| Remaining individualsnot grpmax-eligible | 1.51% | 66 |
| Middle Eastern | 1.14% | 88 |
| Ashkenazi Jewishnot grpmax-eligible | 0.449% | 223 |
| Amishnot grpmax-eligible | 0.439% | 228 |
| European (non-Finnish) | 0.354% | 283 |
| Finnishnot grpmax-eligible | 0.036% | 2,780 |
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.Ala111=
- Coding
- c.333T>C
- MANE Select
- NM_019594
- dbSNP
- rs16930747
- Type
- single nucleotide variant
- Location
- chr9:128907497 (GRCh38)
- Gene constraint
- LOEUF 0.614 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 85.52 · 13 PDB
- Residue 111
- 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-ala111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown