Is CCNF p.Phe480Ile (c.1438T>A) pathogenic?

CCNF p.Phe480Ile (c.1438T>A) is classified Uncertain significance in CCNF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-04). AlphaMissense: likely pathogenic (0.616); Very rare (popmax 0.000177%, nfe).

How common is CCNF p.Phe480Ile (c.1438T>A) in the general population?

CCNF p.Phe480Ile (c.1438T>A) is very rare (popmax 0.000177%, nfe) (gnomAD).

What do computational predictors say about CCNF p.Phe480Ile (c.1438T>A)?

AlphaMissense predicts likely pathogenic (score 0.616) — an in-silico prediction, not a clinical call.

CCNF p.Phe480Ile

c.1438T>A · rs2505769196 · VCV1703946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.616 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000177%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.616	likely pathogenic
REVEL	0.415	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 8,082 bp · p 0.66 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000177% European (non-Finnish) · 2/1,126,948 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000145% 2/1,380,486 alleles · very rare

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.Phe480Ile
Coding: c.1438T>A
MANE Select: NM_001761
dbSNP: rs2505769196
Type: single nucleotide variant
Location: chr16:2449866 (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-phe480ile (accessed [today's date]).

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