Is LRBA p.Arg2134Ser (c.6400C>A) pathogenic?

LRBA p.Arg2134Ser (c.6400C>A) is classified Uncertain significance in LRBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-14). AlphaMissense: likely pathogenic (0.8927); Very rare (popmax 0.00936%, afr); Associated with Inborn genetic diseases.

What condition is associated with LRBA p.Arg2134Ser (c.6400C>A)?

LRBA p.Arg2134Ser (c.6400C>A) is associated with Inborn genetic diseases, combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Arg2134Ser (c.6400C>A) in the general population?

LRBA p.Arg2134Ser (c.6400C>A) is very rare (popmax 0.00936%, afr) (gnomAD).

What do computational predictors say about LRBA p.Arg2134Ser (c.6400C>A)?

AlphaMissense predicts likely pathogenic (score 0.8927) — an in-silico prediction, not a clinical call.

LRBA p.Arg2134Ser

c.6400C>A · rs757445725 · VCV1972788

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8927 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8927	likely pathogenic
REVEL	0.619	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R2145S vs ClinVar R2134S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00936% African / African-American · 7/74,790 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000559% 9/1,609,388 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00936%	10,684
East Asian	0.00447%	22,372

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.Arg2134Ser
Coding: c.6400C>A
MANE Select: NM_001364905
dbSNP: rs757445725
Type: single nucleotide variant
Location: chr4:150490966 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: combined immunodeficiency due to LRBA deficiency

Similar variants

LRBA p.Arg2134Cys Uncertain significance ★★ ⚠ same residue
LRBA p.Arg2134His Uncertain significance ★ same residue
LRBA p.Arg2134del 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

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-arg2134ser (accessed [today's date]).

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