Is CCNO p.Ala123Val (c.368C>T) pathogenic?

CCNO p.Ala123Val (c.368C>T) is classified Uncertain significance in CCNO (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-17). AlphaMissense: likely benign (0.129); Very rare (popmax 0.00196%, amr); Associated with primary ciliary dyskinesia 29.

What condition is associated with CCNO p.Ala123Val (c.368C>T)?

CCNO p.Ala123Val (c.368C>T) is associated with primary ciliary dyskinesia 29 (ClinVar).

How common is CCNO p.Ala123Val (c.368C>T) in the general population?

CCNO p.Ala123Val (c.368C>T) is very rare (popmax 0.00196%, 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.Ala123Val (c.368C>T)?

AlphaMissense predicts likely benign (score 0.129) — an in-silico prediction, not a clinical call.

CCNO p.Ala123Val

c.368C>T · rs1217893462 · VCV1032118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.129 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 29

Computational evidence

Protein change
AlphaMissense	0.129	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -5.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.87	donor gain · deltas
Pangolin	Δ0.54	gain · loss 0.26 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.3	GERP 0.83, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	35.0	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 0.00196% Admixed American · 1/50,908 alleles

Overall 7.18e-05% 1/1,392,150 alleles · very rare

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.Ala123Val
Coding: c.368C>T
MANE Select: NM_021147
dbSNP: rs1217893462
Type: single nucleotide variant
Location: chr5:55233156 (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 29 — 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.Arg133Leu Uncertain significance ★★ ⚠ same condition
CCNO p.Phe164Ser Uncertain significance ★★ ⚠ same condition
CCNO p.Pro89Ala Uncertain significance ★★ ⚠ same condition
CCNO p.Ser63Pro Uncertain significance ★★ ⚠ same condition
CCNO p.Lys319= Benign/Likely benign ★★ same condition
CCNO p.Gln127Ter Pathogenic ★ same condition
CCNO p.Gln321Ter Likely pathogenic ★ 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-ala123val (accessed [today's date]).

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