Is CCNO p.Pro45His (c.134C>A) pathogenic?

CCNO p.Pro45His (c.134C>A) is classified Conflicting classifications of pathogenicity in CCNO (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0812); Rare (popmax 0.249%, amr); Associated with primary ciliary dyskinesia 29.

What condition is associated with CCNO p.Pro45His (c.134C>A)?

CCNO p.Pro45His (c.134C>A) is associated with primary ciliary dyskinesia 29, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Pro45His (c.134C>A) in the general population?

CCNO p.Pro45His (c.134C>A) is rare (popmax 0.249%, amr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CCNO p.Pro45His (c.134C>A)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

CCNO p.Pro45His

c.134C>A · rs139606873 · VCV416791

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.249%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 29

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.90	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 6.1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	24.4	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 0.249% Admixed American · 149/59,866 alleles

Filtering AF 0.216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.134% 2,155/1,610,664 alleles · rare exomes 1,933/1,458,366 · genomes 222/152,298 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.249%	402
European (non-Finnish)	0.159%	629
Remaining individualsnot grpmax-eligible	0.112%	890
Finnishnot grpmax-eligible	0.0611%	1,638
African / African-American	0.0293%	3,409

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.Pro45His
Coding: c.134C>A
MANE Select: NM_021147
dbSNP: rs139606873
Type: single nucleotide variant
Location: chr5:55233390 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06
Residue 45: the 'disordered' region

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

Disease context

primary ciliary dyskinesia 29 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

CCNO p.Pro45= Likely benign ★ same residue
CCNO p.Pro45Ala 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

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-pro45his (accessed [today's date]).

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