Is NFKB2 p.Pro760= (c.2280G>A) pathogenic?

NFKB2 p.Pro760= (c.2280G>A) is classified Likely benign in NFKB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-16). Very rare (popmax 0.00535%, afr); Associated with immunodeficiency, common variable, 10.

What condition is associated with NFKB2 p.Pro760= (c.2280G>A)?

NFKB2 p.Pro760= (c.2280G>A) is associated with immunodeficiency, common variable, 10 (ClinVar).

How common is NFKB2 p.Pro760= (c.2280G>A) in the general population?

NFKB2 p.Pro760= (c.2280G>A) is very rare (popmax 0.00535%, afr) (gnomAD).

NFKB2 p.Pro760=

c.2280G>A · VCV4810885

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Conditions

immunodeficiency, common variable, 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -11	GERP -2.9
Overall
CADD	0.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00535% African / African-American · 4/74,792 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00093% 15/1,612,600 alleles · very rare exomes 11/1,460,798 · genomes 4/151,802 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,698
Admixed American	0.00333%	29,986
South Asian	0.0011%	91,038
European (non-Finnish)	0.000678%	147,475

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: NFKB2
Protein: p.Pro760=
Coding: c.2280G>A
MANE Select: NM_001322934
Type: single nucleotide variant
Location: chr10:102401505 (GRCh38)
Gene constraint: LOEUF 0.308 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.94 · 11 PDB
Residue 760: a UniProt-annotated variant site (in truncated form eb308); a UniProt-annotated variant site (in truncated form p80ht); a UniProt-annotated variant site (in truncated form lb40)

Full NFKB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency, common variable, 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NFKB2 p.Pro760Leu Uncertain significance ★ ⚠ same residue
NFKB2 p.Pro760Ser Uncertain significance ★ ⚠ same residue
NFKB2 p.Arg853Ter Pathogenic ★★ same condition
NFKB2 p.Asp865Gly Pathogenic/Likely pathogenic ★★ same condition
NFKB2 p.Gln871Ter Pathogenic ★★ same condition
NFKB2 c.243+3G>A Uncertain significance ★★ same condition
NFKB2 p.Ala121Thr Uncertain significance ★★ ⚠ same condition
NFKB2 p.Ala363Thr 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/nfkb2-p-pro760 (accessed [today's date]).

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