Is IKBKB p.Phe601= (c.1803C>T) pathogenic?

IKBKB p.Phe601= (c.1803C>T) is classified Likely benign in IKBKB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Very rare (popmax 0.000932%, nfe); Associated with severe combined immunodeficiency due to IKK2 deficiency.

What condition is associated with IKBKB p.Phe601= (c.1803C>T)?

IKBKB p.Phe601= (c.1803C>T) is associated with severe combined immunodeficiency due to IKK2 deficiency (ClinVar).

How common is IKBKB p.Phe601= (c.1803C>T) in the general population?

IKBKB p.Phe601= (c.1803C>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

IKBKB p.Phe601=

Q: How is Combined immunodeficiency due to IKBKB deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1803C>T · rs200019365 · VCV1080878

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Conditions

severe combined immunodeficiency due to IKK2 deficiency

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 · C>A here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.7	GERP -3.2
Overall
CADD	4.655	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,976 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000752% 11/1,461,868 alleles · very rare

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: IKBKB
Protein: p.Phe601=
Coding: c.1803C>T
MANE Select: NM_001556
dbSNP: rs200019365
Type: single nucleotide variant
Location: chr8:42322118 (GRCh38)
Gene constraint: LOEUF 0.472 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.09 · 5 PDB
Residue 601: an α-helix

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

Disease context

severe combined immunodeficiency due to IKK2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to IKBKB deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

IKBKB p.Arg286Ter Pathogenic ★★ same condition
IKBKB p.Val203Ile Pathogenic ★★ ⚠ same condition
IKBKB p.Ala132Val Uncertain significance ★★ ⚠ same condition
IKBKB p.Ala422Thr Uncertain significance ★★ ⚠ same condition
IKBKB p.Ala454Thr Uncertain significance ★★ ⚠ same condition
IKBKB p.Ala702Thr Uncertain significance ★★ ⚠ same condition
IKBKB p.Arg105Trp Uncertain significance ★★ ⚠ same condition
IKBKB p.Arg419Gly 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/ikbkb-p-phe601 (accessed [today's date]).

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