Is LRBA p.Ser1091= (c.3273A>G) pathogenic?

LRBA p.Ser1091= (c.3273A>G) is classified Benign in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-24). Ultra-rare (popmax 0.0944%, sas); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Ser1091= (c.3273A>G)?

LRBA p.Ser1091= (c.3273A>G) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Ser1091= (c.3273A>G) in the general population?

LRBA p.Ser1091= (c.3273A>G) is ultra-rare (popmax 0.0944%, sas) (gnomAD).

LRBA p.Ser1091=

Q: How is Syndromic autoimmune enteropathy due to LRBA deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.3273A>G · rs572733441 · VCV1169537

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0944%, sas)

Conditions

combined immunodeficiency due to LRBA deficiency

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 -0.24	GERP -5.1, phastCons 0.52
Overall
CADD	5.476	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0944% South Asian · 86/91,078 alleles

Filtering AF 0.0782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0723%

Overall 0.00607% 98/1,613,596 alleles · ultra-rare exomes 93/1,461,264 · genomes 5/152,332 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0944%	1,059
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	0.000424%	235,998

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: LRBA
Protein: p.Ser1091=
Coding: c.3273A>G
MANE Select: NM_001364905
dbSNP: rs572733441
Type: single nucleotide variant
Location: chr4:150852437 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)

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

Disease context

combined immunodeficiency due to LRBA deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Syndromic autoimmune enteropathy due to LRBA deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

LRBA p.Ser1091Leu Uncertain significance ★ ⚠ same residue
LRBA c.216+1G>C Pathogenic/Likely pathogenic ★★ same condition
LRBA c.2259-2A>G Likely pathogenic ★★ same condition
LRBA c.2767-2A>G Likely pathogenic ★★ same condition
LRBA c.4159-1G>T Likely pathogenic ★★ same condition
LRBA c.5518+2T>C Likely pathogenic ★★ same condition
LRBA c.5519-1G>A Likely pathogenic ★★ same condition
LRBA c.5646-2A>T Pathogenic ★★ 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/lrba-p-ser1091 (accessed [today's date]).

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