Is CCNO p.Leu213Pro (c.638T>C) pathogenic?

CCNO p.Leu213Pro (c.638T>C) is classified Pathogenic in CCNO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely pathogenic (0.9925); Very rare (popmax 0.000867%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with CCNO p.Leu213Pro (c.638T>C)?

CCNO p.Leu213Pro (c.638T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Leu213Pro (c.638T>C) in the general population?

CCNO p.Leu213Pro (c.638T>C) is very rare (popmax 0.000867%, nfe) (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.Leu213Pro (c.638T>C)?

AlphaMissense predicts likely pathogenic (score 0.9925) — an in-silico prediction, not a clinical call.

CCNO p.Leu213Pro

c.638T>C · rs775051461 · VCV411594

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9925 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000867%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.9925	likely pathogenic ✓ concordant with ClinVar · top 1% in CCNO
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -17.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	33.0	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 0.000867% European (non-Finnish) · 10/1,152,792 alleles

Filtering AF 0.000439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00032%

Overall 0.00333% 52/1,559,878 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.118%	844
Remaining individualsnot grpmax-eligible	0.0132%	7,554
European (non-Finnish)grpmax	0.000867%	115,279

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu213Pro
Coding: c.638T>C
MANE Select: NM_021147
dbSNP: rs775051461
Type: single nucleotide variant
Location: chr5:55231790 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06
Residue 213: a UniProt-annotated variant site (in cild29; decreases formation of basal bodies in multiciliated cells)

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-leu213pro (accessed [today's date]).

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