Is NCF4 p.Ala102= (c.306C>T) pathogenic?

NCF4 p.Ala102= (c.306C>T) is classified Likely benign in NCF4 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-28). Very rare (popmax 0.00667%, amr); Associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3.

How common is NCF4 p.Ala102= (c.306C>T) in the general population?

NCF4 p.Ala102= (c.306C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

How is Chronic granulomatous disease inherited?

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

NCF4 p.Ala102=

Q: What condition is associated with NCF4 p.Ala102= (c.306C>T)?

NCF4 p.Ala102= (c.306C>T) is associated with granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 (ClinVar).

c.306C>T · rs34072404 · VCV539180

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3

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 -20	GERP -2.6
Overall
CADD	0.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,008 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00161% 26/1,614,050 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
African / African-American	0.00267%	37,459
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00153%	65,557
South Asian	0.0011%	91,074

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: NCF4
Protein: p.Ala102=
Coding: c.306C>T
MANE Select: NM_000631
dbSNP: rs34072404
Type: single nucleotide variant
Location: chr22:36867426 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.48 · 6 PDB
Residue 102: the px domain; an α-helix

Full NCF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 — 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

NCF4 p.Ala102Thr Uncertain significance ★ ⚠ same residue
NCF4 c.118-1G>A Pathogenic/Likely pathogenic ★★ same condition
NCF4 c.759-40C>T Pathogenic ★★ same condition
NCF4 p.Arg105Gln Pathogenic ★★ same condition
NCF4 c.758+24C>T Uncertain significance ★★ same condition
NCF4 c.758+32G>A Uncertain significance ★★ same condition
NCF4 c.758+39T>A Uncertain significance ★★ same condition
NCF4 c.758+51G>A 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/ncf4-p-ala102 (accessed [today's date]).

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