Is NFKB2 p.Pro423= (c.1269A>G) pathogenic?

NFKB2 p.Pro423= (c.1269A>G) is classified Benign/Likely benign in NFKB2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency, common variable, 10.

What condition is associated with NFKB2 p.Pro423= (c.1269A>G)?

NFKB2 p.Pro423= (c.1269A>G) is associated with immunodeficiency, common variable, 10 (ClinVar).

NFKB2 p.Pro423=

Q: How common is NFKB2 p.Pro423= (c.1269A>G) in the general population?

NFKB2 p.Pro423= (c.1269A>G) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1269A>G · rs4919633 · VCV403233

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

immunodeficiency, common variable, 10

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.1	GERP -3.1
Overall
CADD	2.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 39,534/39,534 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 99.8% 1,511,918/1,515,066 alleles · common exomes 1,361,164/1,362,752 · genomes 150,754/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
Finnishnot grpmax-eligible	100%	1
European (non-Finnish)	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
South Asian	100%	1
Middle Eastern	99.8%	1
Remaining individualsnot grpmax-eligible	99.7%	1
Amishnot grpmax-eligible	99.7%	1
Admixed American	99.7%	1
African / African-American	96.3%	1

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.Pro423=
Coding: c.1269A>G
MANE Select: NM_001322934
dbSNP: rs4919633
Type: single nucleotide variant
Location: chr10:102399439 (GRCh38)

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

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-pro423 (accessed [today's date]).

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