Is CCDC40 p.Ser598fs (c.1791del) pathogenic?

CCDC40 p.Ser598fs (c.1791del) is classified Likely pathogenic in CCDC40 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). Associated with primary ciliary dyskinesia 15.

What condition is associated with CCDC40 p.Ser598fs (c.1791del)?

CCDC40 p.Ser598fs (c.1791del) is associated with primary ciliary dyskinesia 15 (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

CCDC40 p.Ser598fs

c.1791del · VCV4293979

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

primary ciliary dyskinesia 15

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 11 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP 1.9, phastCons 0.13

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

Variant & gene context

Gene: CCDC40
Protein: p.Ser598fs
Coding: c.1791del
MANE Select: NM_017950
Type: Deletion
Location: chr17:80081774 (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

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

CCDC40 c.2449+2_2449+5del Pathogenic/Likely pathogenic ★★ same condition
CCDC40 p.Ala83fs Pathogenic ★★ same condition
CCDC40 p.Gln524fs Pathogenic ★★ same condition
CCDC40 p.Ile473fs Pathogenic ★★ same condition
CCDC40 p.Lys918fs Pathogenic/Likely pathogenic ★★ same condition
CCDC40 p.Phe1044fs Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.2832+332_2832+395del Benign/Likely benign ★★ same condition
CCDC40 c.1160-2_1162del 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-ser598fs (accessed [today's date]).

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