Is CCNF p.His464= (c.1392C>T) pathogenic?

CCNF p.His464= (c.1392C>T) is classified Benign in CCNF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.573%, afr).

How common is CCNF p.His464= (c.1392C>T) in the general population?

CCNF p.His464= (c.1392C>T) is rare (popmax 0.573%, afr) (gnomAD).

CCNF p.His464=

c.1392C>T · rs147242999 · VCV714682

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.573%, afr)

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 -10	GERP -3.2
Overall
CADD	0.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.573% African / African-American · 430/75,028 alleles

Filtering AF 0.528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.511%

Overall 0.0325% 522/1,603,862 alleles · rare exomes 275/1,451,554 · genomes 247/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.573%	174
Admixed American	0.0534%	1,873
Remaining individualsnot grpmax-eligible	0.0513%	1,950
Middle Eastern	0.0335%	2,988
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,464
South Asian	0.0033%	30,310
European (non-Finnish)	0.00187%	53,601

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: CCNF
Protein: p.His464=
Coding: c.1392C>T
MANE Select: NM_001761
dbSNP: rs147242999
Type: single nucleotide variant
Location: chr16:2449455 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB

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

Similar variants

CCNF p.Ser621Gly Pathogenic/Likely pathogenic ★★ ⚠ same type
CCNF p.Arg140Gln Uncertain significance ★★ ⚠ same type
CCNF p.Arg24Lys Uncertain significance ★★ ⚠ same type
CCNF p.Arg572Gln Uncertain significance ★★ ⚠ same type
CCNF p.Gly254Ala Uncertain significance ★★ ⚠ same type
CCNF p.Gly719Val Uncertain significance ★★ ⚠ same type
CCNF c.1095-28A>G Benign ★★ same type
CCNF c.1095-7G>A Benign ★★ 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/ccnf-p-his464 (accessed [today's date]).

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