Is CCNO p.Ala202Val (c.605C>T) pathogenic?

CCNO p.Ala202Val (c.605C>T) is classified Uncertain significance in CCNO (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-19). AlphaMissense: likely benign (0.2905); Ultra-rare (popmax 0.0844%, afr); Associated with Inborn genetic diseases.

What condition is associated with CCNO p.Ala202Val (c.605C>T)?

CCNO p.Ala202Val (c.605C>T) is associated with Inborn genetic diseases, primary ciliary dyskinesia (ClinVar).

How common is CCNO p.Ala202Val (c.605C>T) in the general population?

CCNO p.Ala202Val (c.605C>T) is ultra-rare (popmax 0.0844%, afr) (gnomAD).

What do computational predictors say about CCNO p.Ala202Val (c.605C>T)?

AlphaMissense predicts likely benign (score 0.2905) — an in-silico prediction, not a clinical call.

CCNO p.Ala202Val

c.605C>T · rs143998638 · VCV648954

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2905 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0844%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2905	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.78	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 6.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,145 bp · p 0.0026 · regional, not allelic
Overall
CADD	25.7	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 0.0844% African / African-American · 62/73,426 alleles

Filtering AF 0.0676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0615%

Overall 0.00504% 78/1,548,906 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0844%	1,184
Remaining individualsnot grpmax-eligible	0.0134%	7,476
Admixed American	0.00581%	17,203
South Asian	0.00356%	28,100
European (non-Finnish)	0.000175%	572,872

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.Ala202Val
Coding: c.605C>T
MANE Select: NM_021147
dbSNP: rs143998638
Type: single nucleotide variant
Location: chr5:55231823 (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

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.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
CCNO p.Arg196Leu 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-ala202val (accessed [today's date]).

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