Is LRBA p.Arg182Ter (c.544C>T) pathogenic?

LRBA p.Arg182Ter (c.544C>T) is classified Pathogenic in LRBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-13). Very rare (popmax 0.000679%, nfe); Associated with LRBA-related disorder.

What condition is associated with LRBA p.Arg182Ter (c.544C>T)?

LRBA p.Arg182Ter (c.544C>T) is associated with LRBA-related disorder, combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Arg182Ter (c.544C>T) in the general population?

LRBA p.Arg182Ter (c.544C>T) is very rare (popmax 0.000679%, nfe) (gnomAD).

LRBA p.Arg182Ter

c.544C>T · VCV3720595

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000679%, nfe)

Conditions

LRBA-related disorder

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 4 of 57
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP 0.22, phastCons 1
Overall
CADD	39.0	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 0.000679% European (non-Finnish) · 8/1,177,758 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000497% 8/1,610,348 alleles · very rare exomes 8/1,458,230 · genomes 0/152,118 · joint denominator

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.Arg182Ter
Coding: c.544C>T
MANE Select: NM_001364905
Type: single nucleotide variant
Location: chr4:150928521 (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

LRBA-related disorder

Also linked: combined immunodeficiency due to LRBA deficiency

Similar variants

LRBA p.Arg182Gln Uncertain significance ★★ ⚠ 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
LRBA c.5646-2A>T 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-arg182ter (accessed [today's date]).

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