Is NFKB2 p.Ser707= (c.2121A>G) pathogenic?

NFKB2 p.Ser707= (c.2121A>G) is classified Likely benign in NFKB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-17). Very rare (popmax 0.00127%, nfe); Associated with immunodeficiency, common variable, 10.

What condition is associated with NFKB2 p.Ser707= (c.2121A>G)?

NFKB2 p.Ser707= (c.2121A>G) is associated with immunodeficiency, common variable, 10 (ClinVar).

How common is NFKB2 p.Ser707= (c.2121A>G) in the general population?

NFKB2 p.Ser707= (c.2121A>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

NFKB2 p.Ser707=

c.2121A>G · VCV4685964

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

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	all four deltas below 0.2 · A>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.7	GERP -3.6
Overall
CADD	0.997	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,177,470 alleles

Filtering AF 0.000765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000607%

Overall 0.000932% 15/1,609,358 alleles · very rare exomes 15/1,457,600 · genomes 0/151,758 · 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: NFKB2
Protein: p.Ser707=
Coding: c.2121A>G
MANE Select: NM_001322934
Type: single nucleotide variant
Location: chr10:102401229 (GRCh38)
Gene constraint: LOEUF 0.308 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.94 · 11 PDB
Residue 707: 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.Ser707Thr 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
NFKB2 p.Ala475Val 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-ser707 (accessed [today's date]).

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