Is CCDC40 p.Ile1002fs (c.3004dup) pathogenic?

CCDC40 p.Ile1002fs (c.3004dup) is classified Pathogenic in CCDC40 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-27). Very rare (popmax 0.00267%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Ile1002fs (c.3004dup)?

CCDC40 p.Ile1002fs (c.3004dup) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 15 (ClinVar).

How common is CCDC40 p.Ile1002fs (c.3004dup) in the general population?

CCDC40 p.Ile1002fs (c.3004dup) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CCDC40 p.Ile1002fs

c.3004dup · rs1278589861 · VCV661903

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 18 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.079	GERP -2.8, phastCons 0.001
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,952 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,080 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,476
Admixed American	0.00167%	60,018

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.Ile1002fs
Coding: c.3004dup
MANE Select: NM_017950
dbSNP: rs1278589861
Type: Duplication
Location: chr17:80095430 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia 15

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.Asn887fs Pathogenic/Likely pathogenic ★★ same condition
CCDC40 p.Lys952fs Pathogenic ★★ same condition
CCDC40 c.2832+395dup Likely pathogenic ★ same condition
CCDC40 p.Arg359fs Pathogenic ★ same condition
CCDC40 p.Arg412fs Pathogenic ★ same condition
CCDC40 p.Asp982fs Pathogenic ★ same condition
CCDC40 p.Glu1032Ter Likely pathogenic ★ same condition
CCDC40 p.Glu1096fs 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-ile1002fs (accessed [today's date]).

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