Is CCNF p.Lys97Arg (c.290A>G) pathogenic?

CCNF p.Lys97Arg (c.290A>G) is classified Uncertain significance in CCNF (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.0756); Very rare (popmax 0.00763%, nfe); Associated with polyneuropathy.

What condition is associated with CCNF p.Lys97Arg (c.290A>G)?

CCNF p.Lys97Arg (c.290A>G) is associated with polyneuropathy (ClinVar).

How common is CCNF p.Lys97Arg (c.290A>G) in the general population?

CCNF p.Lys97Arg (c.290A>G) is very rare (popmax 0.00763%, nfe) (gnomAD).

What do computational predictors say about CCNF p.Lys97Arg (c.290A>G)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

CCNF p.Lys97Arg

c.290A>G · rs1465313712 · VCV982987

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

polyneuropathy

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.59	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 6	GERP -0.21, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 19 kb · p 0.0017 · regional, not allelic
Overall
CADD	19.7	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

Grpmax group 0.00763% European (non-Finnish) · 90/1,179,716 alleles

Filtering AF 0.00631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00584%

Overall 0.00595% 96/1,613,510 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00763%	13,108
Remaining individualsnot grpmax-eligible	0.0048%	20,817
Finnishnot grpmax-eligible	0.00313%	31,991
African / African-American	0.00134%	74,886

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.Lys97Arg
Coding: c.290A>G
MANE Select: NM_001761
dbSNP: rs1465313712
Type: single nucleotide variant
Location: chr16:2435817 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 97: a UniProt-annotated variant site (in ftdals5; uncertain significance; impaired degradation by the ubiquitin proteasome system (ups))

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

Disease context

polyneuropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-lys97arg (accessed [today's date]).

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