Is CCNF p.Arg24Lys (c.71G>A) pathogenic?

CCNF p.Arg24Lys (c.71G>A) is classified Uncertain significance in CCNF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-28). AlphaMissense: likely benign (0.1232); Very rare (popmax 0.00167%, amr).

How common is CCNF p.Arg24Lys (c.71G>A) in the general population?

CCNF p.Arg24Lys (c.71G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CCNF p.Arg24Lys (c.71G>A)?

AlphaMissense predicts likely benign (score 0.1232) — an in-silico prediction, not a clinical call.

CCNF p.Arg24Lys

c.71G>A · rs2065260644 · VCV1015932

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1232 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1232	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.34	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 4.3	GERP 0.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 19 kb · p 0.0017 · regional, not allelic
Overall
CADD	14.94	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 0.00167% Admixed American · 1/60,012 alleles

Overall 6.84e-05% 1/1,461,848 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.Arg24Lys
Coding: c.71G>A
MANE Select: NM_001761
dbSNP: rs2065260644
Type: single nucleotide variant
Location: chr16:2431184 (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.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
CCNF c.1218+32T>C 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-arg24lys (accessed [today's date]).

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