Is CCNO p.Ser63Pro (c.187T>C) pathogenic?

CCNO p.Ser63Pro (c.187T>C) is classified Uncertain significance in CCNO (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-02-27). AlphaMissense: likely benign (0.1968); Ultra-rare (popmax 0.0895%, nfe); Associated with primary ciliary dyskinesia 29.

What condition is associated with CCNO p.Ser63Pro (c.187T>C)?

CCNO p.Ser63Pro (c.187T>C) is associated with primary ciliary dyskinesia 29, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Ser63Pro (c.187T>C) in the general population?

CCNO p.Ser63Pro (c.187T>C) is ultra-rare (popmax 0.0895%, 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.Ser63Pro (c.187T>C)?

AlphaMissense predicts likely benign (score 0.1968) — an in-silico prediction, not a clinical call.

CCNO p.Ser63Pro

c.187T>C · rs377241996 · VCV648428

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1968 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0895%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 29

Computational evidence

Protein change
AlphaMissense	0.1968	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.98	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 4.5	GERP 0.47, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	23.2	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 0.0895% European (non-Finnish) · 1,054/1,177,732 alleles

Filtering AF 0.085% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0832%

Overall 0.0678% 1,089/1,606,404 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0895%	1,117
Remaining individualsnot grpmax-eligible	0.029%	3,453
African / African-American	0.0134%	7,485
Admixed American	0.00838%	11,927
East Asian	0.00224%	44,636
Finnishnot grpmax-eligible	0.00165%	60,722

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.Ser63Pro
Coding: c.187T>C
MANE Select: NM_021147
dbSNP: rs377241996
Type: single nucleotide variant
Location: chr5:55233337 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06
Residue 63: 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.Ser63Tyr 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-ser63pro (accessed [today's date]).

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