Is NCF4 p.Phe320= (c.960C>T) pathogenic?

NCF4 p.Phe320= (c.960C>T) is classified Benign/Likely benign in NCF4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-28). Common (popmax 10.5%, afr) — too common for a highly-penetrant pathogenic allele.

NCF4 p.Phe320=

Q: How common is NCF4 p.Phe320= (c.960C>T) in the general population?

NCF4 p.Phe320= (c.960C>T) is common (popmax 10.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.960C>T · rs1858 · VCV1288899

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 10.5%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.11	GERP -1.6, phastCons 0.002
Overall
CADD	7.577	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.5% African / African-American · 7,836/74,970 alleles

Filtering AF 10.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.2%

Overall 0.934% 15,075/1,614,018 alleles · common exomes 9,924/1,461,836 · genomes 5,151/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.5%	10
Middle Eastern	6.58%	15
Admixed American	1.79%	56
Remaining individualsnot grpmax-eligible	1.69%	59
Ashkenazi Jewishnot grpmax-eligible	1.55%	64
European (non-Finnish)	0.334%	300
South Asian	0.331%	303
Amishnot grpmax-eligible	0.329%	304
Finnishnot grpmax-eligible	0.00937%	10,672

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.Phe320=
Coding: c.960C>T
MANE Select: NM_000631
dbSNP: rs1858
Type: single nucleotide variant
Location: chr22:36877763 (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 320: the pb1 domain

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

Similar variants

NCF4 c.118-1G>A Pathogenic/Likely pathogenic ★★ same type
NCF4 c.759-40C>T Pathogenic ★★ same type
NCF4 p.Arg105Gln Pathogenic ★★ same type
NCF4 c.758+24C>T Uncertain significance ★★ same type
NCF4 c.758+32G>A Uncertain significance ★★ same type
NCF4 c.758+39T>A Uncertain significance ★★ same type
NCF4 c.758+51G>A Uncertain significance ★★ same type
NCF4 c.758+62C>T Uncertain significance ★★ same type

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-phe320 (accessed [today's date]).

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