Is LRBA p.Pro1820= (c.5460T>G) pathogenic?

LRBA p.Pro1820= (c.5460T>G) is classified Likely benign in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). Ultra-rare (popmax 0.0157%, eas); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Pro1820= (c.5460T>G)?

LRBA p.Pro1820= (c.5460T>G) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Pro1820= (c.5460T>G) in the general population?

LRBA p.Pro1820= (c.5460T>G) is ultra-rare (popmax 0.0157%, eas) (gnomAD).

LRBA p.Pro1820=

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.5460T>G · rs565770808 · VCV540412

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, eas)

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	0.083	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8	GERP 2.8, phastCons 1
Overall
CADD	12.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0157% East Asian · 7/44,462 alleles

Filtering AF 0.00732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00518%

Overall 0.00087% 14/1,609,198 alleles · ultra-rare exomes 13/1,456,940 · genomes 1/152,258 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0157%	6,352
Remaining individualsnot grpmax-eligible	0.00321%	31,135
South Asian	0.00111%	90,308
European (non-Finnish)	0.00034%	294,425

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.Pro1820=
Coding: c.5460T>G
MANE Select: NM_001364905
dbSNP: rs565770808
Type: single nucleotide variant
Location: chr4:150806329 (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.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
LRBA p.Arg1445Ter 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-pro1820 (accessed [today's date]).

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