Is NCF2 p.Arg66fs (c.196_197insA) pathogenic?

NCF2 p.Arg66fs (c.196197insA) is classified Likely pathogenic in NCF2 (ClinVar, Single submitter, 1 submitter). Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2.

What condition is associated with NCF2 p.Arg66fs (c.196_197insA)?

NCF2 p.Arg66fs (c.196_197insA) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (ClinVar).

How is Chronic granulomatous disease inherited?

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

NCF2 p.Arg66fs

c.196_197insA · VCV3382464

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.55	GERP -0.95, phastCons 0.76

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: NCF2
Protein: p.Arg66fs
Coding: c.196_197insA
MANE Select: NM_000433
Type: Insertion
Location: chr1:183586955 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 7 PDB
Residue 66: an α-helix

Full NCF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Chronic granulomatous disease (Orphanet):

Inheritance: Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

NCF2 p.Arg66Ter Pathogenic ★★ same residue
NCF2 p.Arg66= Conflicting classifications of pathogenicity ★ same residue
NCF2 p.Arg66Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
NCF2 c.257+1G>A Pathogenic/Likely pathogenic ★★ same condition
NCF2 c.366+1G>A Pathogenic ★★ same condition
NCF2 c.714-2A>G Likely pathogenic ★★ same condition
NCF2 p.Ala140fs Pathogenic/Likely pathogenic ★★ same condition
NCF2 p.Ala202Val Pathogenic/Likely pathogenic ★★ 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/ncf2-p-arg66fs (accessed [today's date]).

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