Is CCDC40 p.Glu428fs (c.1266_1281dup) pathogenic?

CCDC40 p.Glu428fs (c.12661281dup) is classified Pathogenic in CCDC40 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-18). Absent from gnomAD; Associated with primary ciliary dyskinesia 15.

What condition is associated with CCDC40 p.Glu428fs (c.1266_1281dup)?

CCDC40 p.Glu428fs (c.1266_1281dup) is associated with primary ciliary dyskinesia 15 (ClinVar).

How common is CCDC40 p.Glu428fs (c.1266_1281dup) in the general population?

CCDC40 p.Glu428fs (c.1266_1281dup) 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.Glu428fs

c.1266_1281dup · rs2510295924 · VCV2431510

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 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 8 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP 2.1, 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.Glu428fs
Coding: c.1266_1281dup
MANE Select: NM_017950
dbSNP: rs2510295924
Type: Duplication
Location: chr17:80058599 (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 p.Ile1002fs Pathogenic ★★ same condition
CCDC40 c.2832+395dup Likely pathogenic ★ same condition
CCDC40 p.Glu1032Ter Likely pathogenic ★ same condition
CCDC40 p.Glu753fs Likely pathogenic ★ same condition
CCDC40 p.Val279fs Likely pathogenic ★ same condition
CCDC40 c.676+2_676+3dup Conflicting classifications of pathogenicity ★ same condition
CCDC40 c.1159+1G>A Likely pathogenic ★★ same condition
CCDC40 c.2449+2_2449+5del 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-glu428fs (accessed [today's date]).

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