Is CCNO p.Ser32Arg (c.94A>C) pathogenic?

CCNO p.Ser32Arg (c.94A>C) is classified Uncertain significance in CCNO (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-19). AlphaMissense: ambiguous (0.5316); Very rare (popmax 0.00943%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CCNO p.Ser32Arg (c.94A>C)?

CCNO p.Ser32Arg (c.94A>C) is associated with Inborn genetic diseases, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Ser32Arg (c.94A>C) in the general population?

CCNO p.Ser32Arg (c.94A>C) is very rare (popmax 0.00943%, nfe) (gnomAD).

What do computational predictors say about CCNO p.Ser32Arg (c.94A>C)?

AlphaMissense predicts ambiguous (score 0.5316) — an in-silico prediction, not a clinical call.

CCNO p.Ser32Arg

c.94A>C · rs373400250 · VCV411597

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5316 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00943%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5316	ambiguous
REVEL	0.1	moderately benign-leaning
SaProt	LLR -5.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	18.9	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 0.00943% European (non-Finnish) · 111/1,177,618 alleles

Filtering AF 0.00793% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00745%

Overall 0.00709% 114/1,606,962 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00943%	10,609
Remaining individualsnot grpmax-eligible	0.00483%	20,701

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.Ser32Arg
Coding: c.94A>C
MANE Select: NM_021147
dbSNP: rs373400250
Type: single nucleotide variant
Location: chr5:55233430 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06
Residue 32: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

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-ser32arg (accessed [today's date]).

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