LRRC8A p.Cys601=
c.1803T>C · rs16930757 · VCV776452
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.15%, afr)
Conditions
1
agammaglobulinemia 5, autosomal dominant
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7 | GERP -4 |
| Overall | ||
| CADD | 0.453 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.15%
African / African-American · 3,116/75,048 alleles
Filtering AF
4.03%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.98%
Overall
0.278%
4,488/1,614,152 alleles · low-frequency
exomes 2,570/1,461,852 · genomes 1,918/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.15% | 24 |
| Admixed American | 0.457% | 219 |
| East Asian | 0.423% | 236 |
| Remaining individualsnot grpmax-eligible | 0.389% | 257 |
| Middle Eastern | 0.379% | 264 |
| European (non-Finnish) | 0.0523% | 1,913 |
| South Asian | 0.0253% | 3,960 |
| Finnishnot grpmax-eligible | 0.00313% | 31,998 |
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.Cys601=
- Coding
- c.1803T>C
- MANE Select
- NM_019594
- dbSNP
- rs16930757
- Type
- single nucleotide variant
- Location
- chr9:128908967 (GRCh38)
- Gene constraint
- LOEUF 0.614 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 85.52 · 13 PDB
Similar variants
- LRRC8A p.Asp703Asn Uncertain significance ★★ ⚠ same condition
- LRRC8A c.2157+11C>T Benign ★★ same condition
- LRRC8A p.Ala11= Likely benign ★★ same condition
- LRRC8A p.Arg492= Benign ★★ same condition
- LRRC8A p.Asp258= Benign ★★ same condition
- LRRC8A p.Glu665= Benign ★★ same condition
- LRRC8A p.Leu706= Benign ★★ same condition
- LRRC8A p.Pro457= Benign/Likely benign ★★ same condition
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-cys601 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown