Is CCNO p.Arg263Pro (c.788G>C) pathogenic?

CCNO p.Arg263Pro (c.788G>C) is classified Conflicting classifications of pathogenicity in CCNO (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-08-02). AlphaMissense: likely pathogenic (0.7506); Very rare (popmax 0.00684%, eas); Associated with CCNO-related disorder.

What condition is associated with CCNO p.Arg263Pro (c.788G>C)?

CCNO p.Arg263Pro (c.788G>C) is associated with CCNO-related disorder, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Arg263Pro (c.788G>C) in the general population?

CCNO p.Arg263Pro (c.788G>C) is very rare (popmax 0.00684%, eas) (gnomAD).

What do computational predictors say about CCNO p.Arg263Pro (c.788G>C)?

AlphaMissense predicts likely pathogenic (score 0.7506) — an in-silico prediction, not a clinical call.

CCNO p.Arg263Pro

c.788G>C · rs746811253 · VCV411598

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7506 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00684%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCNO-related disorder

Computational evidence

Protein change
AlphaMissense	0.7506	likely pathogenic
REVEL	0.153	moderately benign-leaning
SaProt	LLR -15.74	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -1.7, phastCons 0.12
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	20.6	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 0.00684% East Asian · 3/43,878 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000903%

Overall 0.000277% 4/1,443,712 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00684%	14,626
European (non-Finnish)	8.53e-05%	1,171,886

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.Arg263Pro
Coding: c.788G>C
MANE Select: NM_021147
dbSNP: rs746811253
Type: single nucleotide variant
Location: chr5:55231640 (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

Also linked: primary ciliary dyskinesia

Similar variants

CCNO p.Arg263Trp Uncertain significance ★★ ⚠ same residue
CCNO p.Arg263= Likely benign ★ same residue
CCNO p.Gln103Ter Pathogenic ★★ same condition
CCNO p.Ala14Ser Uncertain significance ★★ ⚠ same condition
CCNO p.Ala202Val Uncertain significance ★★ ⚠ same condition
CCNO p.Ala230Thr Uncertain significance ★★ ⚠ same condition
CCNO p.Ala258Gly Uncertain significance ★★ ⚠ same condition
CCNO p.Arg124Leu Uncertain significance ★★ ⚠ 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-arg263pro (accessed [today's date]).

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