Is LRBA p.Pro2518Ser (c.7552C>T) pathogenic?

LRBA p.Pro2518Ser (c.7552C>T) is classified Uncertain significance in LRBA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-04). AlphaMissense: likely benign (0.0855); Ultra-rare (popmax 0.0147%, afr); Associated with Inborn genetic diseases.

What condition is associated with LRBA p.Pro2518Ser (c.7552C>T)?

LRBA p.Pro2518Ser (c.7552C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRBA p.Pro2518Ser (c.7552C>T) in the general population?

LRBA p.Pro2518Ser (c.7552C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about LRBA p.Pro2518Ser (c.7552C>T)?

AlphaMissense predicts likely benign (score 0.0855) — an in-silico prediction, not a clinical call.

LRBA p.Pro2518Ser

c.7552C>T · rs1286528262 · VCV2283070

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0855 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0855	likely benign
REVEL	0.326	indeterminate
SaProt	—	not scored · why
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	21.6	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P2529S vs ClinVar P2518S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,818 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.000868% 14/1,612,548 alleles · ultra-rare exomes 11/1,460,384 · genomes 3/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,802
Remaining individualsnot grpmax-eligible	0.0032%	31,202
European (non-Finnish)	8.48e-05%	1,179,530

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.Pro2518Ser
Coding: c.7552C>T
MANE Select: NM_001364905
dbSNP: rs1286528262
Type: single nucleotide variant
Location: chr4:150321269 (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-pro2518ser (accessed [today's date]).

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