Is LRBA p.Arg310Ter (c.928C>T) pathogenic?

LRBA p.Arg310Ter (c.928C>T) is classified Pathogenic/Likely pathogenic in LRBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-05). Very rare (popmax 0.00224%, eas); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Arg310Ter (c.928C>T)?

LRBA p.Arg310Ter (c.928C>T) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Arg310Ter (c.928C>T) in the general population?

LRBA p.Arg310Ter (c.928C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

LRBA p.Arg310Ter

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.928C>T · rs1170974293 · VCV3001078

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00224%, 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.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 57
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.9, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,734 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,612,120 alleles · very rare exomes 5/1,459,992 · genomes 0/152,128 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,734
Remaining individualsnot grpmax-eligible	0.0016%	62,416
European (non-Finnish)	0.000255%	392,903

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.Arg310Ter
Coding: c.928C>T
MANE Select: NM_001364905
dbSNP: rs1170974293
Type: single nucleotide variant
Location: chr4:150915694 (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-arg310ter (accessed [today's date]).

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