Is LRBA p.Lys342Arg (c.1025A>G) pathogenic?

LRBA p.Lys342Arg (c.1025A>G) is classified Uncertain significance in LRBA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-13). AlphaMissense: likely benign (0.1922); Ultra-rare (popmax 0.0178%, mid); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Lys342Arg (c.1025A>G)?

LRBA p.Lys342Arg (c.1025A>G) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Lys342Arg (c.1025A>G) in the general population?

LRBA p.Lys342Arg (c.1025A>G) is ultra-rare (popmax 0.0178%, mid) (gnomAD).

What do computational predictors say about LRBA p.Lys342Arg (c.1025A>G)?

AlphaMissense predicts likely benign (score 0.1922) — an in-silico prediction, not a clinical call.

LRBA p.Lys342Arg

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.1025A>G · rs201545103 · VCV999922

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1922 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, mid)

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
AlphaMissense	0.1922	likely benign
REVEL	0.411	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% Middle Eastern · 1/5,620 alleles

Filtering AF 0.00734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.0068% 103/1,514,842 alleles · ultra-rare exomes 94/1,363,562 · genomes 9/151,280 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0178%	5,620
European (non-Finnish)	0.00877%	11,398
African / African-American	0.00279%	35,886
Finnishnot grpmax-eligible	0.00166%	60,226

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.Lys342Arg
Coding: c.1025A>G
MANE Select: NM_001364905
dbSNP: rs201545103
Type: single nucleotide variant
Location: chr4:150914331 (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-lys342arg (accessed [today's date]).

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