Is LRBA p.Phe48Ile (c.142T>A) pathogenic?

LRBA p.Phe48Ile (c.142T>A) is classified Uncertain significance in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.9804); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LRBA p.Phe48Ile (c.142T>A)?

LRBA p.Phe48Ile (c.142T>A) is associated with Inborn genetic diseases (ClinVar).

How common is LRBA p.Phe48Ile (c.142T>A) in the general population?

LRBA p.Phe48Ile (c.142T>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about LRBA p.Phe48Ile (c.142T>A)?

AlphaMissense predicts likely pathogenic (score 0.9804) — an in-silico prediction, not a clinical call.

LRBA p.Phe48Ile

c.142T>A · VCV4623821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9804 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9804	likely pathogenic · top 8% in LRBA
REVEL	0.492	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,036 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,182 alleles · very rare exomes 3/1,461,842 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)grpmax	0.000169%	590,019

Remaining individuals 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.Phe48Ile
Coding: c.142T>A
MANE Select: NM_001364905
Type: single nucleotide variant
Location: chr4:151014501 (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.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
LRBA p.Arg2133His 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-phe48ile (accessed [today's date]).

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