Is CCNF p.Ser704= (c.2112C>T) pathogenic?

CCNF p.Ser704= (c.2112C>T) is classified Likely benign in CCNF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). Ultra-rare (popmax 0.066%, mid); Associated with CCNF-related disorder.

What condition is associated with CCNF p.Ser704= (c.2112C>T)?

CCNF p.Ser704= (c.2112C>T) is associated with CCNF-related disorder (ClinVar).

How common is CCNF p.Ser704= (c.2112C>T) in the general population?

CCNF p.Ser704= (c.2112C>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

CCNF p.Ser704=

c.2112C>T · rs373727270 · VCV3039769

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

CCNF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -3.3
Overall
CADD	1.832	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,058 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.0154% 248/1,613,218 alleles · ultra-rare exomes 199/1,460,862 · genomes 49/152,356 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.4%	29
Middle Easterngrpmax	0.066%	1,514
Remaining individualsnot grpmax-eligible	0.0256%	3,904
Finnishnot grpmax-eligible	0.0235%	4,251
Admixed American	0.0233%	4,283
South Asian	0.0176%	5,687
European (non-Finnish)	0.0126%	7,917
African / African-American	0.004%	25,015

Amish 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.Ser704=
Coding: c.2112C>T
MANE Select: NM_001761
dbSNP: rs373727270
Type: single nucleotide variant
Location: chr16:2456771 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 704: the 'pest' region; the 'disordered' region

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

Disease context

CCNF-related disorder

Similar variants

CCNF c.347-4G>A Likely benign same condition
CCNF p.Ala145= Likely benign same condition
CCNF p.Ala74Thr Benign same condition
CCNF p.Arg349= Likely benign same condition
CCNF p.Leu352= Likely benign same condition
CCNF p.Leu531Arg Likely benign ⚠ same condition
CCNF p.Tyr250= Likely benign same condition
CCNF p.Ser621Gly Pathogenic/Likely pathogenic ★★ ⚠ 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-ser704 (accessed [today's date]).

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