Is CCNF p.Ala145= (c.435C>T) pathogenic?

CCNF p.Ala145= (c.435C>T) is classified Likely benign in CCNF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-30). Ultra-rare (popmax 0.0535%, eas); Associated with CCNF-related disorder.

What condition is associated with CCNF p.Ala145= (c.435C>T)?

CCNF p.Ala145= (c.435C>T) is associated with CCNF-related disorder (ClinVar).

How common is CCNF p.Ala145= (c.435C>T) in the general population?

CCNF p.Ala145= (c.435C>T) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

CCNF p.Ala145=

c.435C>T · rs200978756 · VCV3034783

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

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 -6.3	GERP -3.7
Overall
CADD	1.443	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0535% East Asian · 24/44,850 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00781% 126/1,613,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0743%	1,346
East Asiangrpmax	0.0535%	1,869
Middle Eastern	0.0165%	6,056
South Asian	0.0121%	8,276
Remaining individualsnot grpmax-eligible	0.0112%	8,926
European (non-Finnish)	0.00492%	20,338
Finnishnot grpmax-eligible	0.00315%	31,766
African / African-American	0.00133%	75,054

Ashkenazi Jewish 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.Ala145=
Coding: c.435C>T
MANE Select: NM_001761
dbSNP: rs200978756
Type: single nucleotide variant
Location: chr16:2437217 (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

Disease context

CCNF-related disorder

Similar variants

CCNF c.347-4G>A 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.Ser704= 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-ala145 (accessed [today's date]).

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