Is LRBA p.Asp64Glu (c.192T>G) pathogenic?

LRBA p.Asp64Glu (c.192T>G) is classified Uncertain significance in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-20). AlphaMissense: likely pathogenic (0.7919); Very rare (popmax 0.00237%, nfe); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Asp64Glu (c.192T>G)?

LRBA p.Asp64Glu (c.192T>G) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Asp64Glu (c.192T>G) in the general population?

LRBA p.Asp64Glu (c.192T>G) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about LRBA p.Asp64Glu (c.192T>G)?

AlphaMissense predicts likely pathogenic (score 0.7919) — an in-silico prediction, not a clinical call.

LRBA p.Asp64Glu

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.192T>G · rs1222697259 · VCV580340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
AlphaMissense	0.7919	likely pathogenic
REVEL	0.192	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.19	GERP -2.9, phastCons 0.23
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	19.93	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 0.00237% European (non-Finnish) · 28/1,179,962 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00186% 30/1,614,030 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,141
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,950

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.Asp64Glu
Coding: c.192T>G
MANE Select: NM_001364905
dbSNP: rs1222697259
Type: single nucleotide variant
Location: chr4:151014451 (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.Asp64Gly Uncertain significance ★★ same residue
LRBA p.Asp64= Likely benign ★ 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-asp64glu (accessed [today's date]).

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