Is LRBA p.Val1695Ala (c.5084T>C) pathogenic?

LRBA p.Val1695Ala (c.5084T>C) is classified Uncertain significance in LRBA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-28). AlphaMissense: likely benign (0.0842); Rare (popmax 0.127%, eas); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Val1695Ala (c.5084T>C)?

LRBA p.Val1695Ala (c.5084T>C) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Val1695Ala (c.5084T>C) in the general population?

LRBA p.Val1695Ala (c.5084T>C) is rare (popmax 0.127%, eas) (gnomAD).

What do computational predictors say about LRBA p.Val1695Ala (c.5084T>C)?

AlphaMissense predicts likely benign (score 0.0842) — an in-silico prediction, not a clinical call.

LRBA p.Val1695Ala

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.5084T>C · rs200935054 · VCV473179

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0842 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.127%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
AlphaMissense	0.0842	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.086, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	18.21	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.127% East Asian · 57/44,890 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0911%

Overall 0.00489% 79/1,614,190 alleles · rare exomes 75/1,461,832 · genomes 4/152,358 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.127%	788
Remaining individualsnot grpmax-eligible	0.0336%	2,977
European (non-Finnish)	8.47e-05%	1,179,999

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.Val1695Ala
Coding: c.5084T>C
MANE Select: NM_001364905
dbSNP: rs200935054
Type: single nucleotide variant
Location: chr4:150828267 (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.Val1695= Likely benign ★ 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-val1695ala (accessed [today's date]).

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