Is LRBA p.Val1850= (c.5550T>C) pathogenic?

LRBA p.Val1850= (c.5550T>C) is classified Benign/Likely benign in LRBA (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 24.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Val1850= (c.5550T>C)?

LRBA p.Val1850= (c.5550T>C) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

LRBA p.Val1850=

Q: How common is LRBA p.Val1850= (c.5550T>C) in the general population?

LRBA p.Val1850= (c.5550T>C) is common (popmax 24.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.5550T>C · rs1129998 · VCV403050

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 24.5%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.1	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -1.2, phastCons 1
Overall
CADD	7.373	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.5% European (non-Finnish) · 286,700/1,171,022 alleles

Filtering AF 24.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 24.4%

Overall 21.8% 350,127/1,603,866 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	34.2%	3
Finnishnot grpmax-eligible	28.2%	4
European (non-Finnish)grpmax	24.5%	4
Remaining individualsnot grpmax-eligible	19.7%	5
East Asian	18.7%	5
Middle Eastern	15.9%	6
Ashkenazi Jewishnot grpmax-eligible	12.2%	8
Admixed American	11.6%	9
South Asian	10.9%	9
African / African-American	3.98%	25

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val1850=
Coding: c.5550T>C
MANE Select: NM_001364905
dbSNP: rs1129998
Type: single nucleotide variant
Location: chr4:150798111 (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 p.Val1850Leu 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-val1850 (accessed [today's date]).

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