Is LRBA p.Ile2620Ser (c.7859T>G) pathogenic?

LRBA p.Ile2620Ser (c.7859T>G) is classified Uncertain significance in LRBA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1475); Ultra-rare (popmax 0.0148%, afr); Associated with Inborn genetic diseases.

What condition is associated with LRBA p.Ile2620Ser (c.7859T>G)?

LRBA p.Ile2620Ser (c.7859T>G) is associated with Inborn genetic diseases, combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Ile2620Ser (c.7859T>G) in the general population?

LRBA p.Ile2620Ser (c.7859T>G) is ultra-rare (popmax 0.0148%, afr) (gnomAD).

What do computational predictors say about LRBA p.Ile2620Ser (c.7859T>G)?

AlphaMissense predicts likely benign (score 0.1475) — an in-silico prediction, not a clinical call.

LRBA p.Ile2620Ser

c.7859T>G · rs777084152 · VCV643414

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1475 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1475	likely benign
REVEL	0.173	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 6.1	GERP 0.64, 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

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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I2631S vs ClinVar I2620S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0148% African / African-American · 11/74,278 alleles

Filtering AF 0.00822% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00638%

Overall 0.000753% 12/1,594,636 alleles · ultra-rare exomes 6/1,442,438 · genomes 6/152,198 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0148%	6,753
European (non-Finnish)	8.54e-05%	1,170,877

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.Ile2620Ser
Coding: c.7859T>G
MANE Select: NM_001364905
dbSNP: rs777084152
Type: single nucleotide variant
Location: chr4:150302783 (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

Also linked: combined immunodeficiency due to LRBA deficiency

Similar variants

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
LRBA p.Arg1445Ter 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-ile2620ser (accessed [today's date]).

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