Is LRBA p.Pro816fs (c.2447del) pathogenic?

LRBA p.Pro816fs (c.2447del) is classified Pathogenic in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Pro816fs (c.2447del)?

LRBA p.Pro816fs (c.2447del) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

LRBA p.Pro816fs

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.2447del · VCV3775540

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 20 of 57
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 0.097, phastCons 1

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

Variant & gene context

Gene: LRBA
Protein: p.Pro816fs
Coding: c.2447del
MANE Select: NM_001364905
Type: Deletion
Location: chr4:150870527 (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 c.1923_1924+11del Likely pathogenic ★★ same condition
LRBA p.Asp1329fs Pathogenic/Likely pathogenic ★★ same condition
LRBA p.Glu945_Glu946insTer Pathogenic ★★ same condition
LRBA p.Ser2079fs Pathogenic/Likely pathogenic ★★ same condition
LRBA p.Thr1587fs Likely pathogenic ★★ same condition
LRBA c.1015-10del Benign/Likely benign ★★ same condition
LRBA c.217-10del Benign/Likely benign ★★ same condition
LRBA c.4570-6del 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-pro816fs (accessed [today's date]).

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