Is CCDC40 p.Asp233Asn (c.697G>A) pathogenic?

CCDC40 p.Asp233Asn (c.697G>A) is classified Conflicting classifications of pathogenicity in CCDC40 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-12-03). AlphaMissense: likely benign (0.0776); Rare (popmax 0.249%, mid); Associated with primary ciliary dyskinesia 15.

What condition is associated with CCDC40 p.Asp233Asn (c.697G>A)?

CCDC40 p.Asp233Asn (c.697G>A) is associated with primary ciliary dyskinesia 15, primary ciliary dyskinesia (ClinVar).

How common is CCDC40 p.Asp233Asn (c.697G>A) in the general population?

CCDC40 p.Asp233Asn (c.697G>A) is rare (popmax 0.249%, mid) (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 CCDC40 p.Asp233Asn (c.697G>A)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

CCDC40 p.Asp233Asn

c.697G>A · rs201815496 · VCV583321

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.249%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 15

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.55	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 -1.2	GERP -3.6
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.29 · regional, not allelic
Overall
CADD	3.069	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 0.249% Middle Eastern · 15/6,024 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0268% 433/1,613,598 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.249%	402
South Asian	0.0417%	2,397
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,289
European (non-Finnish)	0.0281%	3,564
Remaining individualsnot grpmax-eligible	0.0272%	3,675
African / African-American	0.0147%	6,819
East Asian	0.0134%	7,478
Admixed American	0.01%	10,004

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: CCDC40
Protein: p.Asp233Asn
Coding: c.697G>A
MANE Select: NM_017950
dbSNP: rs201815496
Type: single nucleotide variant
Location: chr17:80048603 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.70 · 1 PDB

Full CCDC40 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

CCDC40 p.Asp233= Benign/Likely benign ★★ same residue
CCDC40 c.1159+1G>A Likely pathogenic ★★ same condition
CCDC40 c.1989+1G>A Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.2712-1G>T Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.855+1G>A Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.940-1G>C Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.940-2A>G Pathogenic ★★ same condition
CCDC40 p.Arg1059Ter Pathogenic/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/ccdc40-p-asp233asn (accessed [today's date]).

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