Is LRBA p.Arg771Ser (c.2313G>C) pathogenic?

LRBA p.Arg771Ser (c.2313G>C) is classified Uncertain significance in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: likely pathogenic (0.9787); Absent from gnomAD v4.1; Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Arg771Ser (c.2313G>C)?

LRBA p.Arg771Ser (c.2313G>C) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Arg771Ser (c.2313G>C) in the general population?

LRBA p.Arg771Ser (c.2313G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRBA p.Arg771Ser (c.2313G>C)?

AlphaMissense predicts likely pathogenic (score 0.9787) — an in-silico prediction, not a clinical call.

LRBA p.Arg771Ser

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.2313G>C · rs1753425532 · VCV946212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9787 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
AlphaMissense	0.9787	likely pathogenic · top 9% in LRBA
REVEL	0.549	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -0.48, phastCons 0.64
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	21.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LRBA
Protein: p.Arg771Ser
Coding: c.2313G>C
MANE Select: NM_001364905
dbSNP: rs1753425532
Type: single nucleotide variant
Location: chr4:150871399 (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-arg771ser (accessed [today's date]).

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