Is CCNF p.Arg343Trp (c.1027C>T) pathogenic?

CCNF p.Arg343Trp (c.1027C>T) is classified Uncertain significance in CCNF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). AlphaMissense: likely benign (0.127); Ultra-rare (popmax 0.05%, amr).

How common is CCNF p.Arg343Trp (c.1027C>T) in the general population?

CCNF p.Arg343Trp (c.1027C>T) is ultra-rare (popmax 0.05%, amr) (gnomAD).

What do computational predictors say about CCNF p.Arg343Trp (c.1027C>T)?

AlphaMissense predicts likely benign (score 0.127) — an in-silico prediction, not a clinical call.

CCNF p.Arg343Trp

c.1027C>T · VCV4650049

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.127 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.05%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.127	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.71	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 1.6	GERP -2.1, phastCons 0.95
Regional constraint	o/e 0.86	unconstrained · MANE · 19 kb · p 0.0017 · regional, not allelic
Overall
CADD	25.3	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 0.05% Admixed American · 30/59,988 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.00266% 43/1,613,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.05%	2,000
Remaining individualsnot grpmax-eligible	0.0064%	15,620
East Asian	0.00223%	44,886
African / African-American	0.00134%	74,900
European (non-Finnish)	0.000593%	168,573

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.Arg343Trp
Coding: c.1027C>T
MANE Select: NM_001761
Type: single nucleotide variant
Location: chr16:2445555 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 343: the cyclin n-terminal domain; an α-helix

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

Similar variants

CCNF p.Arg343Gln Uncertain significance ★ ⚠ same residue
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

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-arg343trp (accessed [today's date]).

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