Is CCNF p.Leu247Val (c.739C>G) pathogenic?

CCNF p.Leu247Val (c.739C>G) is classified Likely benign in CCNF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: ambiguous (0.4082); Absent from gnomAD v4.1.

How common is CCNF p.Leu247Val (c.739C>G) in the general population?

CCNF p.Leu247Val (c.739C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNF p.Leu247Val (c.739C>G)?

AlphaMissense predicts ambiguous (score 0.4082) — an in-silico prediction, not a clinical call.

CCNF p.Leu247Val

c.739C>G · VCV3264562

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4082 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4082	ambiguous
REVEL	0.191	benign-leaning
SaProt	LLR -11.48	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.67, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 19 kb · p 0.0017 · regional, not allelic
Overall
CADD	24.3	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.Leu247Val
Coding: c.739C>G
MANE Select: NM_001761
Type: single nucleotide variant
Location: chr16:2439788 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 247: 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-leu247val (accessed [today's date]).

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