Is LRBA p.Ser1003= (c.3009T>A) pathogenic?

LRBA p.Ser1003= (c.3009T>A) is classified Likely benign in LRBA (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0848%, nfe); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Ser1003= (c.3009T>A)?

LRBA p.Ser1003= (c.3009T>A) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Ser1003= (c.3009T>A) in the general population?

LRBA p.Ser1003= (c.3009T>A) is ultra-rare (popmax 0.0848%, nfe) (gnomAD).

LRBA p.Ser1003=

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.3009T>A · rs149919062 · VCV790906

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0848%, nfe)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -5.9, phastCons 0.92
Overall
CADD	2.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0848% European (non-Finnish) · 1,001/1,179,934 alleles

Filtering AF 0.0805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.064% 1,033/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0848%	1,179
Remaining individualsnot grpmax-eligible	0.0336%	2,976
African / African-American	0.0107%	9,382
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
Finnishnot grpmax-eligible	0.00312%	32,015

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.Ser1003=
Coding: c.3009T>A
MANE Select: NM_001364905
dbSNP: rs149919062
Type: single nucleotide variant
Location: chr4:150852701 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)
Residue 1003: the 'disordered' region; a modified residue (phosphoserine)

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-ser1003 (accessed [today's date]).

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