Is CCDC40 p.Pro1119Ser (c.3355C>T) pathogenic?

CCDC40 p.Pro1119Ser (c.3355C>T) is classified Uncertain significance in CCDC40 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-08). AlphaMissense: ambiguous (0.4006); Very rare (popmax 0.00223%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Pro1119Ser (c.3355C>T)?

CCDC40 p.Pro1119Ser (c.3355C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC40 p.Pro1119Ser (c.3355C>T) in the general population?

CCDC40 p.Pro1119Ser (c.3355C>T) is very rare (popmax 0.00223%, eas) (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.Pro1119Ser (c.3355C>T)?

AlphaMissense predicts ambiguous (score 0.4006) — an in-silico prediction, not a clinical call.

CCDC40 p.Pro1119Ser

c.3355C>T · rs777697239 · VCV2362526

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.4006	ambiguous
REVEL	0.683	pathogenic-leaning
SaProt	LLR -11.20	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.29 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000806% 13/1,613,720 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000932%	107,275

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.Pro1119Ser
Coding: c.3355C>T
MANE Select: NM_017950
dbSNP: rs777697239
Type: single nucleotide variant
Location: chr17:80099701 (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-pro1119ser (accessed [today's date]).

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