Is CCNF p.Glu396Asp (c.1188G>T) pathogenic?

CCNF p.Glu396Asp (c.1188G>T) is classified Benign in CCNF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: ambiguous (0.4614); Low-frequency (popmax 1.37%, mid).

How common is CCNF p.Glu396Asp (c.1188G>T) in the general population?

CCNF p.Glu396Asp (c.1188G>T) is low-frequency (popmax 1.37%, mid) (gnomAD).

What do computational predictors say about CCNF p.Glu396Asp (c.1188G>T)?

AlphaMissense predicts ambiguous (score 0.4614) — an in-silico prediction, not a clinical call.

CCNF p.Glu396Asp

c.1188G>T · rs36008785 · VCV775366

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4614 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4614	ambiguous
REVEL	0.216	benign-leaning
SaProt	LLR -6.74	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -0.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 8,082 bp · p 0.66 · regional, not allelic
Overall
CADD	22.1	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 1.37% Middle Eastern · 83/6,062 alleles

Filtering AF 1.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.04%

Overall 0.0657% 1,061/1,614,128 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.37%	73
Ashkenazi Jewishnot grpmax-eligible	1.32%	76
Remaining individualsnot grpmax-eligible	0.205%	488
Admixed American	0.0366%	2,729
South Asian	0.0362%	2,760
European (non-Finnish)	0.0326%	3,065
African / African-American	0.02%	5,002
Finnishnot grpmax-eligible	0.00469%	21,340

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.Glu396Asp
Coding: c.1188G>T
MANE Select: NM_001761
dbSNP: rs36008785
Type: single nucleotide variant
Location: chr16:2448948 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 396: 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.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-glu396asp (accessed [today's date]).

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