Is LRBA p.Ser2129= (c.6387A>C) pathogenic?

LRBA p.Ser2129= (c.6387A>C) is classified Benign/Likely benign in LRBA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Rare (popmax 0.335%, afr); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Ser2129= (c.6387A>C)?

LRBA p.Ser2129= (c.6387A>C) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Ser2129= (c.6387A>C) in the general population?

LRBA p.Ser2129= (c.6387A>C) is rare (popmax 0.335%, afr) (gnomAD).

LRBA p.Ser2129=

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.6387A>C · rs144748889 · VCV540405

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.335%, 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	0.024	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -4.1
Overall
CADD	5.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.335% African / African-American · 251/74,974 alleles

Filtering AF 0.301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.287%

Overall 0.0271% 437/1,610,318 alleles · rare exomes 285/1,458,240 · genomes 152/152,078 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.335%	299
Middle Eastern	0.182%	549
Admixed American	0.0617%	1,620
Remaining individualsnot grpmax-eligible	0.0466%	2,148
European (non-Finnish)	0.00892%	11,215
South Asian	0.00442%	22,620

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.Ser2129=
Coding: c.6387A>C
MANE Select: NM_001364905
dbSNP: rs144748889
Type: single nucleotide variant
Location: chr4:150490979 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)
Residue 2129: 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 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
LRBA p.Arg1445Ter 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-ser2129 (accessed [today's date]).

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