Is LRBA p.Ser1772Pro (c.5314T>C) pathogenic?

LRBA p.Ser1772Pro (c.5314T>C) is classified Uncertain significance in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-23). AlphaMissense: likely benign (0.0643); Ultra-rare (popmax 0.0676%, sas); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Ser1772Pro (c.5314T>C)?

LRBA p.Ser1772Pro (c.5314T>C) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Ser1772Pro (c.5314T>C) in the general population?

LRBA p.Ser1772Pro (c.5314T>C) is ultra-rare (popmax 0.0676%, sas) (gnomAD).

What do computational predictors say about LRBA p.Ser1772Pro (c.5314T>C)?

AlphaMissense predicts likely benign (score 0.0643) — an in-silico prediction, not a clinical call.

LRBA p.Ser1772Pro

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.5314T>C · rs534886197 · VCV1435813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0643 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0676%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
AlphaMissense	0.0643	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP -2.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	18.92	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0676% South Asian · 61/90,264 alleles

Filtering AF 0.054% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.049%

Overall 0.00419% 67/1,599,112 alleles · ultra-rare exomes 64/1,446,782 · genomes 3/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0676%	1,480
Remaining individualsnot grpmax-eligible	0.00161%	61,920
European (non-Finnish)	0.000428%	233,475

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.Ser1772Pro
Coding: c.5314T>C
MANE Select: NM_001364905
dbSNP: rs534886197
Type: single nucleotide variant
Location: chr4:150808390 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)
Residue 1772: the 'disordered' region

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-ser1772pro (accessed [today's date]).

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