Is CCNO p.Pro336Leu (c.1007C>T) pathogenic?

CCNO p.Pro336Leu (c.1007C>T) is classified Conflicting classifications of pathogenicity in CCNO (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.3106); Rare (popmax 0.516%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with CCNO p.Pro336Leu (c.1007C>T)?

CCNO p.Pro336Leu (c.1007C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Pro336Leu (c.1007C>T) in the general population?

CCNO p.Pro336Leu (c.1007C>T) is rare (popmax 0.516%, afr) (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.Pro336Leu (c.1007C>T)?

AlphaMissense predicts likely benign (score 0.3106) — an in-silico prediction, not a clinical call.

CCNO p.Pro336Leu

c.1007C>T · rs115697956 · VCV525497

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3106 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.516%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.3106	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -15.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	23.3	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 0.516% African / African-American · 387/75,030 alleles

Filtering AF 0.473% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.457%

Overall 0.0266% 430/1,614,128 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.516%	194
Remaining individualsnot grpmax-eligible	0.0368%	2,718
Admixed American	0.0283%	3,531
European (non-Finnish)	0.000254%	393,338

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.Pro336Leu
Coding: c.1007C>T
MANE Select: NM_021147
dbSNP: rs115697956
Type: single nucleotide variant
Location: chr5:55231421 (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

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

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.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
CCNO p.Arg133Leu 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-pro336leu (accessed [today's date]).

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