Is CCDC40 c.552+5G>A pathogenic?

CCDC40 c.552+5G>A is classified Uncertain significance in CCDC40 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-22). Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia 15.

What condition is associated with CCDC40 c.552+5G>A?

CCDC40 c.552+5G>A is associated with primary ciliary dyskinesia 15 (ClinVar).

How common is CCDC40 c.552+5G>A in the general population?

CCDC40 c.552+5G>A is absent from gnomAD v4.1 (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.552+5G>A

rs2037242772 · VCV890286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

primary ciliary dyskinesia 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	Δ0.65	donor loss · deltas
Pangolin	Δ0.68	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.9	GERP 1.6, phastCons 1
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC40
Coding: c.552+5G>A
MANE Select: NM_017950
dbSNP: rs2037242772
Type: single nucleotide variant
Location: chr17:80040275 (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.1159+1G>A Likely pathogenic ★★ same condition
CCDC40 c.2712-1G>T Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.940-1G>C Pathogenic/Likely 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
CCDC40 p.Arg449Ter Pathogenic ★★ same condition
CCDC40 p.Gln142Ter 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-c-552-plus-5g-a (accessed [today's date]).

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