Is LRBA p.Ile2350= (c.7050C>A) pathogenic?

LRBA p.Ile2350= (c.7050C>A) is classified Likely benign in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). Ultra-rare (popmax 0.0118%, amr); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Ile2350= (c.7050C>A)?

LRBA p.Ile2350= (c.7050C>A) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Ile2350= (c.7050C>A) in the general population?

LRBA p.Ile2350= (c.7050C>A) is ultra-rare (popmax 0.0118%, amr) (gnomAD).

LRBA p.Ile2350=

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.7050C>A · rs760554343 · VCV1084893

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, amr)

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	0.132	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.087	GERP -1.3, phastCons 0.31
Overall
CADD	2.453	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0118% Admixed American · 7/59,524 alleles

Filtering AF 0.00547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00383%

Overall 0.00122% 19/1,557,044 alleles · ultra-rare exomes 19/1,404,964 · genomes 0/152,080 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0118%	8,503
East Asian	0.00225%	44,514
European (non-Finnish)	0.000973%	102,734

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.Ile2350=
Coding: c.7050C>A
MANE Select: NM_001364905
dbSNP: rs760554343
Type: single nucleotide variant
Location: chr4:150415582 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)
Residue 2350: the beach domain; an α-helix

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.Ile2350Val 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-ile2350 (accessed [today's date]).

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