Is NCF2 p.Cys514= (c.1542C>T) pathogenic?

NCF2 p.Cys514= (c.1542C>T) is classified Likely benign in NCF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-03). Very rare (popmax 0.00449%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NCF2 p.Cys514= (c.1542C>T)?

NCF2 p.Cys514= (c.1542C>T) is associated with Inborn genetic diseases, granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (ClinVar).

How common is NCF2 p.Cys514= (c.1542C>T) in the general population?

NCF2 p.Cys514= (c.1542C>T) is very rare (popmax 0.00449%, nfe) (gnomAD).

NCF2 p.Cys514=

c.1542C>T · rs769779675 · VCV756011

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -3.5
Overall
CADD	4.393	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% European (non-Finnish) · 53/1,179,998 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00335% 54/1,613,964 alleles · very rare exomes 49/1,461,860 · genomes 5/152,104 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,264
South Asian	0.0011%	91,084

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.Cys514=
Coding: c.1542C>T
MANE Select: NM_000433
dbSNP: rs769779675
Type: single nucleotide variant
Location: chr1:183556157 (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 514: the sh3 2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

NCF2 p.Cys514Arg Uncertain significance ★ ⚠ 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.Ala202Val Pathogenic/Likely pathogenic ★★ same condition
NCF2 p.Arg102Ter Pathogenic ★★ same condition
NCF2 p.Arg184Ter Pathogenic/Likely pathogenic ★★ same condition
NCF2 p.Arg66Ter 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-cys514 (accessed [today's date]).

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