Is NCF2 p.Arg524fs (c.1569_1573del) pathogenic?

NCF2 p.Arg524fs (c.15691573del) is classified Uncertain significance in NCF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-31). Very rare (popmax 0.00223%, eas); Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2.

What condition is associated with NCF2 p.Arg524fs (c.1569_1573del)?

NCF2 p.Arg524fs (c.1569_1573del) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (ClinVar).

How common is NCF2 p.Arg524fs (c.1569_1573del) in the general population?

NCF2 p.Arg524fs (c.1569_1573del) is very rare (popmax 0.00223%, eas) (gnomAD).

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.Arg524fs

c.1569_1573del · rs2102867375 · VCV1478709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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	escapes	premature termination codon in the last exon (15 of 15) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.37	GERP -3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,840 alleles · very rare exomes 3/1,461,502 · genomes 0/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
European (non-Finnish)	0.00017%	589,849

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: NCF2
Protein: p.Arg524fs
Coding: c.1569_1573del
MANE Select: NM_000433
dbSNP: rs2102867375
Type: Deletion
Location: chr1:183556126 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 7 PDB

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.Ala140fs Pathogenic/Likely pathogenic ★★ same condition
NCF2 p.Lys19_Asp21del Pathogenic ★★ same condition
NCF2 p.Lys391fs Pathogenic ★★ same condition
NCF2 p.Thr279fs Pathogenic ★★ same condition
NCF2 c.258-13del Likely benign ★★ same condition
NCF2 c.855+20del Likely benign ★★ same condition
NCF2 p.Gln367fs Likely pathogenic ★ same condition
NCF2 p.Glu243fs 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-arg524fs (accessed [today's date]).

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