Is CCDC40 p.Ser489= (c.1467C>T) pathogenic?

CCDC40 p.Ser489= (c.1467C>T) is classified Conflicting classifications of pathogenicity in CCDC40 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0354%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Ser489= (c.1467C>T)?

CCDC40 p.Ser489= (c.1467C>T) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 15 (ClinVar).

How common is CCDC40 p.Ser489= (c.1467C>T) in the general population?

CCDC40 p.Ser489= (c.1467C>T) is ultra-rare (popmax 0.0354%, nfe) (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.Ser489=

c.1467C>T · rs200154414 · VCV227211

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0354%, nfe)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.31	GERP -3.8
Overall
CADD	2.512	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0354% European (non-Finnish) · 418/1,179,972 alleles

Filtering AF 0.0325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0315%

Overall 0.0276% 445/1,612,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0354%	2,823
Remaining individualsnot grpmax-eligible	0.0352%	2,840
African / African-American	0.00267%	37,450
East Asian	0.00223%	44,810
Admixed American	0.00167%	59,986
Finnishnot grpmax-eligible	0.00158%	63,176

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
Protein: p.Ser489=
Coding: c.1467C>T
MANE Select: NM_017950
dbSNP: rs200154414
Type: single nucleotide variant
Location: chr17:80065511 (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

Also linked: primary ciliary dyskinesia 15

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.Ser489Arg Uncertain significance ★★ ⚠ same residue
CCDC40 p.Ser489Ile Benign ★★ same residue
CCDC40 p.Ser489fs Pathogenic ★★ same residue
CCDC40 c.1159+1G>A Likely pathogenic ★★ same condition
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

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-ser489 (accessed [today's date]).

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