Is NFKB2 p.Phe728= (c.2184C>T) pathogenic?

NFKB2 p.Phe728= (c.2184C>T) is classified Likely benign in NFKB2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-25). Absent from gnomAD v4.1; Associated with immunodeficiency, common variable, 10.

What condition is associated with NFKB2 p.Phe728= (c.2184C>T)?

NFKB2 p.Phe728= (c.2184C>T) is associated with immunodeficiency, common variable, 10 (ClinVar).

How common is NFKB2 p.Phe728= (c.2184C>T) in the general population?

NFKB2 p.Phe728= (c.2184C>T) is absent from gnomAD v4.1 (gnomAD).

NFKB2 p.Phe728=

c.2184C>T · rs2061240413 · VCV3030910

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

immunodeficiency, common variable, 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.8, phastCons 1
Overall
CADD	11.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NFKB2
Protein: p.Phe728=
Coding: c.2184C>T
MANE Select: NM_001322934
dbSNP: rs2061240413
Type: single nucleotide variant
Location: chr10:102401292 (GRCh38)
Gene constraint: LOEUF 0.308 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.94 · 11 PDB
Residue 728: the 'disordered' region; 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.Phe728Cys Uncertain significance ★ ⚠ same residue
NFKB2 p.Phe728Leu 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-phe728 (accessed [today's date]).

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