Is LRBA p.Ser2446= (c.7338A>T) pathogenic?

LRBA p.Ser2446= (c.7338A>T) is classified Likely benign in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LRBA p.Ser2446= (c.7338A>T)?

LRBA p.Ser2446= (c.7338A>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRBA p.Ser2446= (c.7338A>T) in the general population?

LRBA p.Ser2446= (c.7338A>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

LRBA p.Ser2446=

c.7338A>T · VCV4623830

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.071	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.6	GERP -3.5, phastCons 0.063
Overall
CADD	5.387	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,810 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,796 alleles · very rare exomes 3/1,461,460 · genomes 0/152,336 · 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.Ser2446=
Coding: c.7338A>T
MANE Select: NM_001364905
Type: single nucleotide variant
Location: chr4:150350016 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)
Residue 2446: the beach domain; an α-helix

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-ser2446 (accessed [today's date]).

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