Is CCNF p.Gln302Pro (c.905A>C) pathogenic?

CCNF p.Gln302Pro (c.905A>C) is classified Uncertain significance in CCNF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: ambiguous (0.5495); Absent from gnomAD v4.1; Associated with frontotemporal dementia and/or amyotrophic lateral sclerosis 5.

What condition is associated with CCNF p.Gln302Pro (c.905A>C)?

CCNF p.Gln302Pro (c.905A>C) is associated with frontotemporal dementia and/or amyotrophic lateral sclerosis 5 (ClinVar).

How common is CCNF p.Gln302Pro (c.905A>C) in the general population?

CCNF p.Gln302Pro (c.905A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNF p.Gln302Pro (c.905A>C)?

AlphaMissense predicts ambiguous (score 0.5495) — an in-silico prediction, not a clinical call.

CCNF p.Gln302Pro

Q: How is Frontotemporal dementia with motor neuron disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.905A>C · VCV4277964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5495 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

frontotemporal dementia and/or amyotrophic lateral sclerosis 5

Computational evidence

Protein change
AlphaMissense	0.5495	ambiguous
REVEL	0.545	indeterminate
SaProt	LLR -14.05	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 19 kb · p 0.0017 · regional, not allelic
Overall
CADD	26.1	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

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.Gln302Pro
Coding: c.905A>C
MANE Select: NM_001761
Type: single nucleotide variant
Location: chr16:2443776 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 302: the cyclin n-terminal domain

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

Disease context

frontotemporal dementia and/or amyotrophic lateral sclerosis 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Frontotemporal dementia with motor neuron disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

CCNF p.Ser621Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
CCNF p.Arg572Gln Uncertain significance ★★ ⚠ same condition
CCNF p.Ala146Thr Uncertain significance ★ ⚠ same condition
CCNF p.Arg21Gln Uncertain significance ★ ⚠ same condition
CCNF p.Arg572Leu Uncertain significance ★ ⚠ same condition
CCNF p.Gly161Arg Uncertain significance ★ ⚠ same condition
CCNF p.His69Tyr Uncertain significance ★ ⚠ same condition
CCNF p.Arg392Thr Pathogenic ⚠ 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/ccnf-p-gln302pro (accessed [today's date]).

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