Is CCDC40 p.Thr483= (c.1449C>T) pathogenic?

CCDC40 p.Thr483= (c.1449C>T) is classified Benign in CCDC40 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Common (popmax 5.07%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Thr483= (c.1449C>T)?

CCDC40 p.Thr483= (c.1449C>T) is associated with primary ciliary dyskinesia, 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.Thr483=

Q: How common is CCDC40 p.Thr483= (c.1449C>T) in the general population?

CCDC40 p.Thr483= (c.1449C>T) is common (popmax 5.07%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1449C>T · rs116824266 · VCV226488

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 5.07%, afr) — too common for a highly-penetrant pathogenic allele

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 -10	GERP -3.8
Overall
CADD	0.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.07% African / African-American · 3,800/75,000 alleles

Filtering AF 4.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.88%

Overall 0.264% 4,259/1,613,072 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.07%	20
Remaining individualsnot grpmax-eligible	0.31%	322
Admixed American	0.3%	333
Middle Eastern	0.132%	758
European (non-Finnish)	0.00619%	16,164
South Asian	0.00329%	30,358
East Asian	0.00223%	44,814

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.Thr483=
Coding: c.1449C>T
MANE Select: NM_017950
dbSNP: rs116824266
Type: single nucleotide variant
Location: chr17:80065493 (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 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
CCDC40 c.940-2A>G Pathogenic ★★ same condition
CCDC40 p.Arg1059Ter Pathogenic/Likely pathogenic ★★ same condition
CCDC40 p.Arg301Ter 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-thr483 (accessed [today's date]).

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