Is CCDC40 p.Ser1142Pro (c.3424T>C) pathogenic?

CCDC40 p.Ser1142Pro (c.3424T>C) is classified Benign/Likely benign in CCDC40 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1315); Low-frequency (popmax 1.23%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Ser1142Pro (c.3424T>C)?

CCDC40 p.Ser1142Pro (c.3424T>C) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 15 (ClinVar).

How common is CCDC40 p.Ser1142Pro (c.3424T>C) in the general population?

CCDC40 p.Ser1142Pro (c.3424T>C) is low-frequency (popmax 1.23%, afr) (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.Ser1142Pro (c.3424T>C)?

AlphaMissense predicts likely benign (score 0.1315) — an in-silico prediction, not a clinical call.

CCDC40 p.Ser1142Pro

c.3424T>C · rs148900528 · VCV195521

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1315 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.23%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1315	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.33	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 -1.5	GERP -3
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.29 · regional, not allelic
Overall
CADD	12.07	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 1.23% African / African-American · 919/74,932 alleles

Filtering AF 1.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.0668% 1,078/1,612,568 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.23%	82
Middle Eastern	0.132%	757
Remaining individualsnot grpmax-eligible	0.106%	947
Admixed American	0.0817%	1,224
European (non-Finnish)	0.00288%	34,698
South Asian	0.0022%	45,527

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.Ser1142Pro
Coding: c.3424T>C
MANE Select: NM_017950
dbSNP: rs148900528
Type: single nucleotide variant
Location: chr17:80099770 (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-ser1142pro (accessed [today's date]).

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