Is LRBA p.Ala394Pro (c.1180G>C) pathogenic?

LRBA p.Ala394Pro (c.1180G>C) is classified Uncertain significance in LRBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-16). AlphaMissense: ambiguous (0.5295); Very rare (popmax 0.00335%, amr); Associated with Inborn genetic diseases.

What condition is associated with LRBA p.Ala394Pro (c.1180G>C)?

LRBA p.Ala394Pro (c.1180G>C) is associated with Inborn genetic diseases (ClinVar).

How common is LRBA p.Ala394Pro (c.1180G>C) in the general population?

LRBA p.Ala394Pro (c.1180G>C) is very rare (popmax 0.00335%, amr) (gnomAD).

What do computational predictors say about LRBA p.Ala394Pro (c.1180G>C)?

AlphaMissense predicts ambiguous (score 0.5295) — an in-silico prediction, not a clinical call.

LRBA p.Ala394Pro

c.1180G>C · rs753848083 · VCV1303373

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5295 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00335%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5295	ambiguous
REVEL	0.26	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.24, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	22.9	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 0.00335% Admixed American · 2/59,778 alleles

Filtering AF 0.000555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000124% 2/1,612,320 alleles · very rare exomes 2/1,460,070 · genomes 0/152,250 · joint denominator

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.Ala394Pro
Coding: c.1180G>C
MANE Select: NM_001364905
dbSNP: rs753848083
Type: single nucleotide variant
Location: chr4:150908839 (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.Ala394Val Uncertain significance ★ ⚠ same residue
LRBA p.Ala2007Val 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-ala394pro (accessed [today's date]).

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