Is CCDC40 p.Ala60= (c.180G>A) pathogenic?

CCDC40 p.Ala60= (c.180G>A) is classified Benign/Likely benign in CCDC40 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-24). Rare (popmax 0.599%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Ala60= (c.180G>A)?

CCDC40 p.Ala60= (c.180G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC40 p.Ala60= (c.180G>A) in the general population?

CCDC40 p.Ala60= (c.180G>A) is rare (popmax 0.599%, afr) (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.Ala60=

c.180G>A · rs185006459 · VCV226490

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.599%, afr)

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 -2.6	GERP -3.6
Overall
CADD	3.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.599% African / African-American · 449/74,948 alleles

Filtering AF 0.553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.535%

Overall 0.0317% 512/1,613,776 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.599%	167
Remaining individualsnot grpmax-eligible	0.0496%	2,016
Admixed American	0.0333%	2,999
Middle Eastern	0.0165%	6,062
South Asian	0.00439%	22,765
European (non-Finnish)	0.000593%	168,552

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.Ala60=
Coding: c.180G>A
MANE Select: NM_017950
dbSNP: rs185006459
Type: single nucleotide variant
Location: chr17:80039898 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.70 · 1 PDB
Residue 60: the 'disordered' region

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

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.Ala60Val Uncertain significance ★ ⚠ same residue
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-ala60 (accessed [today's date]).

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