Is CCNO p.Pro89Ala (c.265C>G) pathogenic?

CCNO p.Pro89Ala (c.265C>G) is classified Uncertain significance in CCNO (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-06-13). AlphaMissense: likely benign (0.0576); Ultra-rare (popmax 0.0667%, mid); Associated with Inborn genetic diseases.

What condition is associated with CCNO p.Pro89Ala (c.265C>G)?

CCNO p.Pro89Ala (c.265C>G) is associated with Inborn genetic diseases, primary ciliary dyskinesia 29, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Pro89Ala (c.265C>G) in the general population?

CCNO p.Pro89Ala (c.265C>G) is ultra-rare (popmax 0.0667%, mid) (gnomAD).

What do computational predictors say about CCNO p.Pro89Ala (c.265C>G)?

AlphaMissense predicts likely benign (score 0.0576) — an in-silico prediction, not a clinical call.

CCNO p.Pro89Ala

c.265C>G · rs764171316 · VCV1698884

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0576 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0576	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.79, phastCons 0.51
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	13.29	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0667% Middle Eastern · 4/6,000 alleles

Filtering AF 0.0227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00183% 29/1,588,054 alleles · ultra-rare exomes 26/1,435,854 · genomes 3/152,200 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0667%	1,500
Admixed American	0.00357%	28,020
Remaining individualsnot grpmax-eligible	0.00325%	30,783
European (non-Finnish)	0.00171%	58,488
African / African-American	0.00134%	74,714

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.Pro89Ala
Coding: c.265C>G
MANE Select: NM_021147
dbSNP: rs764171316
Type: single nucleotide variant
Location: chr5:55233259 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06
Residue 89: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia 29 primary ciliary dyskinesia

Similar variants

CCNO p.Pro89Leu Uncertain significance ★ ⚠ 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
CCNO p.Arg124Trp 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-pro89ala (accessed [today's date]).

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