Is LRBA p.Ser2091= (c.6273C>T) pathogenic?

LRBA p.Ser2091= (c.6273C>T) is classified Likely benign in LRBA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-22). Rare (popmax 0.148%, mid); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Ser2091= (c.6273C>T)?

LRBA p.Ser2091= (c.6273C>T) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Ser2091= (c.6273C>T) in the general population?

LRBA p.Ser2091= (c.6273C>T) is rare (popmax 0.148%, mid) (gnomAD).

LRBA p.Ser2091=

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.6273C>T · rs146901365 · VCV809689

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.374	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.9	GERP -5.9
Overall
CADD	4.768	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,078 alleles

Filtering AF 0.0772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0577%

Overall 0.00198% 32/1,612,422 alleles · rare exomes 27/1,460,402 · genomes 5/152,020 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	675
African / African-American	0.00534%	18,714
Admixed American	0.00167%	59,794
Remaining individualsnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)	0.00144%	69,370

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.Ser2091=
Coding: c.6273C>T
MANE Select: NM_001364905
dbSNP: rs146901365
Type: single nucleotide variant
Location: chr4:150588105 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)
Residue 2091: the beach-type ph domain

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.Ser2091Phe 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-ser2091 (accessed [today's date]).

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