Is CCNF p.Trp475Arg (c.1423T>C) pathogenic?

CCNF p.Trp475Arg (c.1423T>C) is classified Uncertain significance in CCNF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.2183); Absent from gnomAD v4.1.

How common is CCNF p.Trp475Arg (c.1423T>C) in the general population?

CCNF p.Trp475Arg (c.1423T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNF p.Trp475Arg (c.1423T>C)?

AlphaMissense predicts likely benign (score 0.2183) — an in-silico prediction, not a clinical call.

CCNF p.Trp475Arg

c.1423T>C · VCV4278657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2183 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2183	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -3.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.41, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 8,082 bp · p 0.66 · regional, not allelic
Overall
CADD	17.24	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCNF
Protein: p.Trp475Arg
Coding: c.1423T>C
MANE Select: NM_001761
Type: single nucleotide variant
Location: chr16:2449851 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 475: an α-helix

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-trp475arg (accessed [today's date]).

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