Is LRRC8A p.Ala11= (c.33G>A) pathogenic?

LRRC8A p.Ala11= (c.33G>A) is classified Likely benign in LRRC8A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.0513%, eas); Associated with agammaglobulinemia 5, autosomal dominant.

What condition is associated with LRRC8A p.Ala11= (c.33G>A)?

LRRC8A p.Ala11= (c.33G>A) is associated with agammaglobulinemia 5, autosomal dominant (ClinVar).

How common is LRRC8A p.Ala11= (c.33G>A) in the general population?

LRRC8A p.Ala11= (c.33G>A) is ultra-rare (popmax 0.0513%, eas) (gnomAD).

LRRC8A p.Ala11=

c.33G>A · rs202218761 · VCV1635972

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0513%, eas)

Conditions

agammaglobulinemia 5, autosomal dominant

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 1.7	GERP -4, phastCons 1
Overall
CADD	14.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0513% East Asian · 23/44,802 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0297%

Overall 0.0121% 195/1,611,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0513%	1,948
South Asian	0.0209%	4,793
Remaining individualsnot grpmax-eligible	0.0144%	6,929
European (non-Finnish)	0.0116%	8,596
African / African-American	0.00533%	18,753
Admixed American	0.005%	19,997

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.Ala11=
Coding: c.33G>A
MANE Select: NM_019594
dbSNP: rs202218761
Type: single nucleotide variant
Location: chr9:128907197 (GRCh38)
Gene constraint: LOEUF 0.614 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 85.52 · 13 PDB

Full LRRC8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

agammaglobulinemia 5, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRRC8A p.Ala11Val Uncertain significance ★ ⚠ same residue
LRRC8A p.Asp703Asn Uncertain significance ★★ ⚠ same condition
LRRC8A c.2157+11C>T Benign ★★ same condition
LRRC8A p.Arg492= Benign ★★ same condition
LRRC8A p.Asp258= Benign ★★ same condition
LRRC8A p.Cys601= Benign ★★ same condition
LRRC8A p.Glu665= Benign ★★ same condition
LRRC8A p.Leu706= 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-ala11 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown