Is NFKB2 p.Pro857= (c.2571C>T) pathogenic?

NFKB2 p.Pro857= (c.2571C>T) is classified Likely benign in NFKB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). Very rare (popmax 8.63e-05%, nfe); Associated with immunodeficiency, common variable, 10.

What condition is associated with NFKB2 p.Pro857= (c.2571C>T)?

NFKB2 p.Pro857= (c.2571C>T) is associated with immunodeficiency, common variable, 10 (ClinVar).

How common is NFKB2 p.Pro857= (c.2571C>T) in the general population?

NFKB2 p.Pro857= (c.2571C>T) is very rare (popmax 8.63e-05%, nfe) (gnomAD).

NFKB2 p.Pro857=

c.2571C>T · rs1342322560 · VCV2199867

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.63e-05%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -1.8
Overall
CADD	8.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.63e-05% European (non-Finnish) · 1/1,158,602 alleles

Overall 0.000127% 2/1,572,892 alleles · very rare exomes 2/1,420,542 · genomes 0/152,350 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00164%	60,956
European (non-Finnish)grpmax	8.63e-05%	1,158,602

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro857=
Coding: c.2571C>T
MANE Select: NM_001322934
dbSNP: rs1342322560
Type: single nucleotide variant
Location: chr10:102402152 (GRCh38)
Gene constraint: LOEUF 0.308 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.94 · 11 PDB
Residue 857: 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.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
NFKB2 p.Ala572Thr 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-pro857 (accessed [today's date]).

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