Is CCDC40 c.855+10C>T pathogenic?

CCDC40 c.855+10C>T is classified Benign/Likely benign in CCDC40 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Rare (popmax 0.289%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 c.855+10C>T?

CCDC40 c.855+10C>T is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC40 c.855+10C>T in the general population?

CCDC40 c.855+10C>T is rare (popmax 0.289%, sas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

CCDC40 c.855+10C>T

rs376261068 · VCV700908

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.289%, sas)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +10	near-intronic (+10 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.4	GERP -3.3
Non-coding constraint	Z 1.24	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	0.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.289% South Asian · 258/89,292 alleles

Filtering AF 0.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.249%

Overall 0.0194% 311/1,600,138 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.289%	346
Middle Eastern	0.0827%	1,209
Remaining individualsnot grpmax-eligible	0.0193%	5,168
European (non-Finnish)	0.00298%	33,521
East Asian	0.00226%	44,252

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
Coding: c.855+10C>T
MANE Select: NM_017950
dbSNP: rs376261068
Type: single nucleotide variant
Location: chr17:80048771 (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 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
CCDC40 p.Arg301Ter Pathogenic/Likely pathogenic ★★ same condition
CCDC40 p.Arg321Ter 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-c-855-plus-10c-t (accessed [today's date]).

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