Is CCNO p.Pro6Thr (c.16C>A) pathogenic?

CCNO p.Pro6Thr (c.16C>A) is classified Uncertain significance in CCNO (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-05). AlphaMissense: likely benign (0.079); Ultra-rare (popmax 0.0174%, amr); Associated with CCNO-related disorder.

What condition is associated with CCNO p.Pro6Thr (c.16C>A)?

CCNO p.Pro6Thr (c.16C>A) is associated with CCNO-related disorder, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Pro6Thr (c.16C>A) in the general population?

CCNO p.Pro6Thr (c.16C>A) is ultra-rare (popmax 0.0174%, amr) (gnomAD).

What do computational predictors say about CCNO p.Pro6Thr (c.16C>A)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

CCNO p.Pro6Thr

c.16C>A · rs1299342018 · VCV857554

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCNO-related disorder

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.28	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 1.4	GERP -1.2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	17.71	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 0.0174% Admixed American · 10/57,514 alleles

Filtering AF 0.00936% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.00082% 13/1,584,572 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0174%	5,751
Remaining individualsnot grpmax-eligible	0.00328%	30,514
Finnishnot grpmax-eligible	0.00174%	57,574

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.Pro6Thr
Coding: c.16C>A
MANE Select: NM_021147
dbSNP: rs1299342018
Type: single nucleotide variant
Location: chr5:55233508 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06
Residue 6: the 'disordered' region

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

Disease context

CCNO-related disorder

Also linked: primary ciliary dyskinesia

Similar variants

CCNO p.Pro6= Likely benign ★ 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-pro6thr (accessed [today's date]).

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