Is CCNO p.Val265fs (c.793dup) pathogenic?

CCNO p.Val265fs (c.793dup) is classified Likely pathogenic in CCNO (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-29). Very rare (popmax 0.00332%, nfe); Associated with CCNO-related disorder.

What condition is associated with CCNO p.Val265fs (c.793dup)?

CCNO p.Val265fs (c.793dup) is associated with CCNO-related disorder (ClinVar).

How common is CCNO p.Val265fs (c.793dup) in the general population?

CCNO p.Val265fs (c.793dup) is very rare (popmax 0.00332%, nfe) (gnomAD).

CCNO p.Val265fs

c.793dup · VCV4970387

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00332%, nfe)

Conditions

CCNO-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00332% European (non-Finnish) · 39/1,173,632 alleles

Filtering AF 0.00249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00218%

Overall 0.00263% 42/1,598,918 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00332%	30,093
Finnishnot grpmax-eligible	0.00323%	30,918
Remaining individualsnot grpmax-eligible	0.00162%	61,822

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: CCNO
Protein: p.Val265fs
Coding: c.793dup
MANE Select: NM_021147
Type: Duplication
Location: chr5:55231634 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06

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

Disease context

CCNO-related disorder

Similar variants

CCNO p.Gly85fs Pathogenic ★★ same condition
CCNO p.Val180fs Pathogenic/Likely pathogenic ★★ same condition
CCNO p.Val265Leu Uncertain significance ★ ⚠ same residue
CCNO p.Val265Met Uncertain significance ★ ⚠ same residue
CCNO p.Gln88fs Pathogenic ★★ same condition
CCNO p.Gly229Ser Uncertain significance ★★ ⚠ same condition
CCNO p.Pro6Thr Uncertain significance ★★ ⚠ same condition
CCNO p.Arg133Cys Likely pathogenic ★ same condition

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/ccno-p-val265fs (accessed [today's date]).

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