Is LRBA p.Pro1790= (c.5370G>A) pathogenic?

LRBA p.Pro1790= (c.5370G>A) is classified Likely benign in LRBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-11). Ultra-rare (popmax 0.0683%, sas); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Pro1790= (c.5370G>A)?

LRBA p.Pro1790= (c.5370G>A) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Pro1790= (c.5370G>A) in the general population?

LRBA p.Pro1790= (c.5370G>A) is ultra-rare (popmax 0.0683%, sas) (gnomAD).

LRBA p.Pro1790=

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.5370G>A · rs762034243 · VCV1094045

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0683%, sas)

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	0.014	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.057	GERP -4.5, phastCons 0.83
Overall
CADD	11.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0683% South Asian · 62/90,736 alleles

Filtering AF 0.0546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0497%

Overall 0.00497% 80/1,611,216 alleles · ultra-rare exomes 73/1,459,046 · genomes 7/152,170 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0683%	1,463
Remaining individualsnot grpmax-eligible	0.00801%	12,478
Admixed American	0.00334%	29,951
East Asian	0.00224%	44,724
European (non-Finnish)	0.000849%	117,812

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.Pro1790=
Coding: c.5370G>A
MANE Select: NM_001364905
dbSNP: rs762034243
Type: single nucleotide variant
Location: chr4:150808334 (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.Pro1790Leu 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-pro1790 (accessed [today's date]).

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