Is LRBA p.Thr596= (c.1788G>A) pathogenic?

LRBA p.Thr596= (c.1788G>A) is classified Uncertain significance in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-17). Very rare (popmax 0.00167%, amr); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Thr596= (c.1788G>A)?

LRBA p.Thr596= (c.1788G>A) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Thr596= (c.1788G>A) in the general population?

LRBA p.Thr596= (c.1788G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

LRBA p.Thr596=

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.1788G>A · rs771544628 · VCV2078907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ1.00	acceptor gain · deltas
Pangolin	Δ0.86	gain · loss 0.73 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.34	GERP -3.6, phastCons 0.94
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,942 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,612,916 alleles · very rare exomes 4/1,460,736 · genomes 0/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,942
African / African-American	0.00133%	74,968
European (non-Finnish)	0.00017%	589,630

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.Thr596=
Coding: c.1788G>A
MANE Select: NM_001364905
dbSNP: rs771544628
Type: single nucleotide variant
Location: chr4:150900185 (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.Thr596Met 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-thr596 (accessed [today's date]).

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