Is CCDC40 p.Gln342Arg (c.1025A>G) pathogenic?

CCDC40 p.Gln342Arg (c.1025A>G) is classified Uncertain significance in CCDC40 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely benign (0.2717); Ultra-rare (popmax 0.0197%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Gln342Arg (c.1025A>G)?

CCDC40 p.Gln342Arg (c.1025A>G) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC40 p.Gln342Arg (c.1025A>G) in the general population?

CCDC40 p.Gln342Arg (c.1025A>G) is ultra-rare (popmax 0.0197%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CCDC40 p.Gln342Arg (c.1025A>G)?

AlphaMissense predicts likely benign (score 0.2717) — an in-silico prediction, not a clinical call.

CCDC40 p.Gln342Arg

c.1025A>G · rs201057426 · VCV1376807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2717 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0197%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.2717	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.29 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0197% European (non-Finnish) · 233/1,180,012 alleles

Filtering AF 0.0176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.0151% 244/1,613,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0197%	5,064
Middle Eastern	0.0165%	6,068
Remaining individualsnot grpmax-eligible	0.0096%	10,413
South Asian	0.0022%	45,545
Admixed American	0.00167%	60,004
African / African-American	0.00133%	74,936

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.Gln342Arg
Coding: c.1025A>G
MANE Select: NM_017950
dbSNP: rs201057426
Type: single nucleotide variant
Location: chr17:80050149 (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

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.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
CCDC40 p.Arg321Ter 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-gln342arg (accessed [today's date]).

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