Is LRBA p.Ser1584fs (c.4750dup) pathogenic?

LRBA p.Ser1584fs (c.4750dup) is classified Pathogenic in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Absent from gnomAD; Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Ser1584fs (c.4750dup)?

LRBA p.Ser1584fs (c.4750dup) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Ser1584fs (c.4750dup) in the general population?

LRBA p.Ser1584fs (c.4750dup) is absent from gnomAD (gnomAD).

LRBA p.Ser1584fs

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.4750dup · rs2546423436 · VCV2018538

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 30 of 57
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.56	GERP 1.2, phastCons 0.061

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LRBA
Protein: p.Ser1584fs
Coding: c.4750dup
MANE Select: NM_001364905
dbSNP: rs2546423436
Type: Duplication
Location: chr4:150828600 (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.Asn2716fs Pathogenic/Likely pathogenic ★★ same condition
LRBA p.Leu2836_Phe2837insLeu Uncertain significance ★★ same condition
LRBA c.1015-10dup Benign/Likely benign ★★ same condition
LRBA c.2068-19dup Benign/Likely benign ★★ same condition
LRBA c.217-10dup Benign ★★ same condition
LRBA c.217-11_217-10dup Benign/Likely benign ★★ same condition
LRBA c.5581-5dup Benign/Likely benign ★★ same condition
LRBA c.5755-10dup Benign/Likely benign ★★ 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-ser1584fs (accessed [today's date]).

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