Is NFKB2 p.Pro613Ser (c.1837C>T) pathogenic?

NFKB2 p.Pro613Ser (c.1837C>T) is classified Uncertain significance in NFKB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-08). AlphaMissense: likely benign (0.1562); Absent from gnomAD v4.1; Associated with immunodeficiency, common variable, 10.

What condition is associated with NFKB2 p.Pro613Ser (c.1837C>T)?

NFKB2 p.Pro613Ser (c.1837C>T) is associated with immunodeficiency, common variable, 10 (ClinVar).

How common is NFKB2 p.Pro613Ser (c.1837C>T) in the general population?

NFKB2 p.Pro613Ser (c.1837C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NFKB2 p.Pro613Ser (c.1837C>T)?

AlphaMissense predicts likely benign (score 0.1562) — an in-silico prediction, not a clinical call.

NFKB2 p.Pro613Ser

c.1837C>T · rs2544597618 · VCV2756247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1562 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency, common variable, 10

Computational evidence

Protein change
AlphaMissense	0.1562	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,079 bp · p 0.0022 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro613Ser
Coding: c.1837C>T
MANE Select: NM_001322934
dbSNP: rs2544597618
Type: single nucleotide variant
Location: chr10:102400693 (GRCh38)
Gene constraint: LOEUF 0.308 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.94 · 11 PDB
Residue 613: an α-helix

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-pro613ser (accessed [today's date]).

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