Is LRBA p.Val2380Phe (c.7138G>T) pathogenic?

LRBA p.Val2380Phe (c.7138G>T) is classified Uncertain significance in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely pathogenic (0.9799); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LRBA p.Val2380Phe (c.7138G>T)?

LRBA p.Val2380Phe (c.7138G>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRBA p.Val2380Phe (c.7138G>T) in the general population?

LRBA p.Val2380Phe (c.7138G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRBA p.Val2380Phe (c.7138G>T)?

AlphaMissense predicts likely pathogenic (score 0.9799) — an in-silico prediction, not a clinical call.

LRBA p.Val2380Phe

c.7138G>T · VCV3867894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9799 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9799	likely pathogenic · top 8% in LRBA
REVEL	0.852	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V2391F vs ClinVar V2380F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LRBA
Protein: p.Val2380Phe
Coding: c.7138G>T
MANE Select: NM_001364905
Type: single nucleotide variant
Location: chr4:150415494 (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

Similar variants

LRBA p.Val2380= Likely benign ★★ same residue
LRBA p.Ala2007Val Uncertain significance ★★ same condition
LRBA p.Ala394Pro Uncertain significance ★★ same condition
LRBA p.Ala627Thr Uncertain significance ★★ ⚠ same condition
LRBA p.Arg1305Pro Uncertain significance ★★ ⚠ same condition
LRBA p.Arg1505Gly Uncertain significance ★★ ⚠ same condition
LRBA p.Arg167Ser Uncertain significance ★★ ⚠ same condition
LRBA p.Arg2128Leu Uncertain significance ★★ ⚠ 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-val2380phe (accessed [today's date]).

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