Is CCDC40 p.Arg412fs (c.1233dup) pathogenic?

CCDC40 p.Arg412fs (c.1233dup) is classified Pathogenic in CCDC40 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-09). Absent from gnomAD; Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Arg412fs (c.1233dup)?

CCDC40 p.Arg412fs (c.1233dup) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC40 p.Arg412fs (c.1233dup) in the general population?

CCDC40 p.Arg412fs (c.1233dup) is absent from gnomAD (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.Arg412fs

c.1233dup · rs2510295858 · VCV1756199

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 8 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 1.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCDC40
Protein: p.Arg412fs
Coding: c.1233dup
MANE Select: NM_017950
dbSNP: rs2510295858
Type: Duplication
Location: chr17:80058566 (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

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.Arg412Gly Uncertain significance ★★ ⚠ same residue
CCDC40 p.Asn887fs Pathogenic/Likely pathogenic ★★ same condition
CCDC40 p.Ile1002fs Pathogenic ★★ same condition
CCDC40 p.Lys952fs Pathogenic ★★ same condition
CCDC40 p.Arg359fs Pathogenic ★ same condition
CCDC40 p.Asp982fs Pathogenic ★ same condition
CCDC40 p.Glu1096fs Pathogenic ★ same condition
CCDC40 p.Met833fs 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-arg412fs (accessed [today's date]).

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