LRRC8A p.His253=
c.759T>C · rs143671130 · VCV1593171
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.124%, 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 -6.8 | GERP -4 |
| Overall | ||
| CADD | 3.086 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.124%
African / African-American · 93/74,868 alleles
Filtering AF
0.104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0962%
Overall
0.00601%
97/1,613,890 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.124% | 805 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| Admixed American | 0.00167% | 59,982 |
| European (non-Finnish) | 8.47e-05% | 1,180,002 |
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.His253=
- Coding
- c.759T>C
- MANE Select
- NM_019594
- dbSNP
- rs143671130
- Type
- single nucleotide variant
- Location
- chr9:128907923 (GRCh38)
- Gene constraint
- LOEUF 0.614 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 85.52 · 13 PDB
- Residue 253
- 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-his253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown