Is CCNF p.Val714Met (c.2140G>A) pathogenic?

CCNF p.Val714Met (c.2140G>A) is classified Benign in CCNF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0828); Low-frequency (popmax 1.64%, nfe).

How common is CCNF p.Val714Met (c.2140G>A) in the general population?

CCNF p.Val714Met (c.2140G>A) is low-frequency (popmax 1.64%, nfe) (gnomAD).

What do computational predictors say about CCNF p.Val714Met (c.2140G>A)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

CCNF p.Val714Met

c.2140G>A · rs61755288 · VCV774504

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.64%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.58	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 -1.3	GERP -2.3
Regional constraint	o/e 0.98	unconstrained · MANE · 8,082 bp · p 0.66 · regional, not allelic
Overall
CADD	6.39	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

Grpmax group 1.64% European (non-Finnish) · 19,363/1,179,954 alleles

Filtering AF 1.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.61%

Overall 1.36% 22,008/1,613,880 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.35%	43
European (non-Finnish)grpmax	1.64%	61
Amishnot grpmax-eligible	1.1%	91
Remaining individualsnot grpmax-eligible	0.999%	100
Ashkenazi Jewishnot grpmax-eligible	0.341%	293
African / African-American	0.266%	375
Admixed American	0.252%	397
South Asian	0.0637%	1,570
Middle Eastern	0.0165%	6,058

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val714Met
Coding: c.2140G>A
MANE Select: NM_001761
dbSNP: rs61755288
Type: single nucleotide variant
Location: chr16:2456799 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 714: the 'pest' region; the 'disordered' region

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

Similar variants

CCNF p.Val714Gly 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-val714met (accessed [today's date]).

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