Is LRBA p.Asp1657= (c.4971T>C) pathogenic?

LRBA p.Asp1657= (c.4971T>C) is classified Likely benign in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Very rare (popmax 0.000508%, nfe); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Asp1657= (c.4971T>C)?

LRBA p.Asp1657= (c.4971T>C) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Asp1657= (c.4971T>C) in the general population?

LRBA p.Asp1657= (c.4971T>C) is very rare (popmax 0.000508%, nfe) (gnomAD).

LRBA p.Asp1657=

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.4971T>C · rs2546422284 · VCV2803565

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

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	0.008	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP -5.6
Overall
CADD	1.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,179,966 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,012 alleles · very rare exomes 7/1,461,826 · genomes 0/152,186 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,016
European (non-Finnish)grpmax	0.000508%	196,661

Finnish 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.Asp1657=
Coding: c.4971T>C
MANE Select: NM_001364905
dbSNP: rs2546422284
Type: single nucleotide variant
Location: chr4:150828380 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)
Residue 1657: 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 p.Asp1657Val 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-asp1657 (accessed [today's date]).

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