Is LRBA p.Ser2468= (c.7404T>C) pathogenic?

LRBA p.Ser2468= (c.7404T>C) is classified Benign/Likely benign in LRBA (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-23). Rare (popmax 0.629%, afr); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Ser2468= (c.7404T>C)?

LRBA p.Ser2468= (c.7404T>C) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Ser2468= (c.7404T>C) in the general population?

LRBA p.Ser2468= (c.7404T>C) is rare (popmax 0.629%, afr) (gnomAD).

LRBA p.Ser2468=

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.7404T>C · rs150550923 · VCV540407

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.629%, afr)

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	0.086	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP 1.7, phastCons 0.37
Overall
CADD	6.788	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.629% African / African-American · 472/75,008 alleles

Filtering AF 0.582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.564%

Overall 0.0328% 529/1,613,538 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.629%	159
Remaining individualsnot grpmax-eligible	0.048%	2,082
Admixed American	0.0384%	2,607
Middle Eastern	0.0165%	6,046
South Asian	0.0011%	91,050
European (non-Finnish)	0.00017%	589,838

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.Ser2468=
Coding: c.7404T>C
MANE Select: NM_001364905
dbSNP: rs150550923
Type: single nucleotide variant
Location: chr4:150325857 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)
Residue 2468: the beach domain; an α-helix

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.Ser2468Phe 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-ser2468 (accessed [today's date]).

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