Is CCDC40 p.Phe868= (c.2604C>T) pathogenic?

CCDC40 p.Phe868= (c.2604C>T) is classified Benign in CCDC40 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-25). Common (popmax 5.93%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Phe868= (c.2604C>T)?

CCDC40 p.Phe868= (c.2604C>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.Phe868=

Q: How common is CCDC40 p.Phe868= (c.2604C>T) in the general population?

CCDC40 p.Phe868= (c.2604C>T) is common (popmax 5.93%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2604C>T · rs61749027 · VCV226491

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 5.93%, 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	<0.2	all four deltas below 0.2 · C>G here scores Δ0.76 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -2.5
Overall
CADD	7.689	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.93% African / African-American · 4,445/75,012 alleles

Filtering AF 5.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.72%

Overall 0.329% 5,303/1,614,038 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.93%	17
Middle Eastern	0.496%	202
Remaining individualsnot grpmax-eligible	0.426%	235
Admixed American	0.413%	242
South Asian	0.0373%	2,678
European (non-Finnish)	0.0232%	4,306
Finnishnot grpmax-eligible	0.00937%	10,672

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.Phe868=
Coding: c.2604C>T
MANE Select: NM_017950
dbSNP: rs61749027
Type: single nucleotide variant
Location: chr17:80087761 (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-phe868 (accessed [today's date]).

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