Is CCDC40 p.Ala894= (c.2682G>A) pathogenic?

CCDC40 p.Ala894= (c.2682G>A) is classified Benign/Likely benign in CCDC40 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Low-frequency (popmax 4.93%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Ala894= (c.2682G>A)?

CCDC40 p.Ala894= (c.2682G>A) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 15 (ClinVar).

How common is CCDC40 p.Ala894= (c.2682G>A) in the general population?

CCDC40 p.Ala894= (c.2682G>A) is low-frequency (popmax 4.93%, eas) (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.Ala894=

c.2682G>A · rs4889815 · VCV260962

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.93%, eas)

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 -1	GERP -2.7
Overall
CADD	5.833	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.93% East Asian · 2,212/44,866 alleles

Filtering AF 4.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.69%

Overall 1.11% 17,924/1,613,594 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	4.93%	20
Admixed American	2.34%	43
Finnishnot grpmax-eligible	2.08%	48
Remaining individualsnot grpmax-eligible	1.06%	95
European (non-Finnish)	0.96%	104
African / African-American	0.533%	188
Ashkenazi Jewishnot grpmax-eligible	0.527%	190
South Asian	0.469%	213
Middle Eastern	0.198%	505

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.Ala894=
Coding: c.2682G>A
MANE Select: NM_017950
dbSNP: rs4889815
Type: single nucleotide variant
Location: chr17:80088073 (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.Ala894Thr Uncertain significance ★ ⚠ same residue
CCDC40 p.Ala894Val Uncertain significance ★ ⚠ 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
CCDC40 c.940-2A>G 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-ala894 (accessed [today's date]).

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