Is LRBA p.Thr780= (c.2340A>G) pathogenic?

LRBA p.Thr780= (c.2340A>G) is classified Conflicting classifications of pathogenicity in LRBA (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-02). Rare (popmax 0.299%, nfe); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Thr780= (c.2340A>G)?

LRBA p.Thr780= (c.2340A>G) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Thr780= (c.2340A>G) in the general population?

LRBA p.Thr780= (c.2340A>G) is rare (popmax 0.299%, nfe) (gnomAD).

LRBA p.Thr780=

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.2340A>G · rs79392371 · VCV289382

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.299%, nfe)

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.26	GERP -3.6, phastCons 0.52
Overall
CADD	6.481	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.299% European (non-Finnish) · 3,516/1,176,784 alleles

Filtering AF 0.291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.287%

Overall 0.226% 3,643/1,610,266 alleles · rare exomes 3,465/1,457,946 · genomes 178/152,320 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.299%	335
Remaining individualsnot grpmax-eligible	0.0882%	1,133
African / African-American	0.056%	1,786
Finnishnot grpmax-eligible	0.0266%	3,762
Admixed American	0.02%	5,001
South Asian	0.0011%	90,870

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.Thr780=
Coding: c.2340A>G
MANE Select: NM_001364905
dbSNP: rs79392371
Type: single nucleotide variant
Location: chr4:150871372 (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.Thr780Ser Uncertain significance ★ ⚠ same residue
LRBA p.Thr780Ala 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

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-thr780 (accessed [today's date]).

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