Is CCNO p.Arg36His (c.107G>A) pathogenic?

CCNO p.Arg36His (c.107G>A) is classified Likely benign in CCNO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.2087); Rare (popmax 0.224%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with CCNO p.Arg36His (c.107G>A)?

CCNO p.Arg36His (c.107G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Arg36His (c.107G>A) in the general population?

CCNO p.Arg36His (c.107G>A) is rare (popmax 0.224%, afr) (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.Arg36His (c.107G>A)?

AlphaMissense predicts likely benign (score 0.2087) — an in-silico prediction, not a clinical call.

CCNO p.Arg36His

c.107G>A · rs142265745 · VCV525469

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2087 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.224%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.2087	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -7.61	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 2.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	24.5	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 0.224% African / African-American · 168/74,970 alleles

Filtering AF 0.196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.186%

Overall 0.0119% 192/1,608,434 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.224%	446
Admixed American	0.0218%	4,586
Middle Eastern	0.0166%	6,022
Remaining individualsnot grpmax-eligible	0.00804%	12,440
South Asian	0.00111%	90,346
European (non-Finnish)	0.000339%	294,564

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.Arg36His
Coding: c.107G>A
MANE Select: NM_021147
dbSNP: rs142265745
Type: single nucleotide variant
Location: chr5:55233417 (GRCh38)
Gene constraint: LOEUF 1.698 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06
Residue 36: the 'disordered' region

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-arg36his (accessed [today's date]).

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