Is CCDC39 p.Pro652Ser (c.1954C>T) pathogenic?

CCDC39 p.Pro652Ser (c.1954C>T) is classified Conflicting classifications of pathogenicity in CCDC39 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.2805); Rare (popmax 0.431%, afr); Associated with primary ciliary dyskinesia 14.

What condition is associated with CCDC39 p.Pro652Ser (c.1954C>T)?

CCDC39 p.Pro652Ser (c.1954C>T) is associated with primary ciliary dyskinesia 14, primary ciliary dyskinesia (ClinVar).

How common is CCDC39 p.Pro652Ser (c.1954C>T) in the general population?

CCDC39 p.Pro652Ser (c.1954C>T) is rare (popmax 0.431%, 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 CCDC39 p.Pro652Ser (c.1954C>T)?

AlphaMissense predicts likely benign (score 0.2805) — an in-silico prediction, not a clinical call.

CCDC39 p.Pro652Ser

c.1954C>T · rs145506099 · VCV667082

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2805 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.431%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 14

Computational evidence

Protein change
AlphaMissense	0.2805	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -6.83	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 64 kb · p 0.72 · regional, not allelic
Overall
CADD	27.8	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 0.431% African / African-American · 323/74,954 alleles

Filtering AF 0.392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.377%

Overall 0.0237% 381/1,608,182 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.431%	232
Remaining individualsnot grpmax-eligible	0.0433%	2,311
Admixed American	0.0417%	2,399
Middle Eastern	0.033%	3,031
East Asian	0.00446%	22,422
South Asian	0.0011%	90,976
European (non-Finnish)	8.48e-05%	1,178,984

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: CCDC39
Protein: p.Pro652Ser
Coding: c.1954C>T
MANE Select: NM_181426
dbSNP: rs145506099
Type: single nucleotide variant
Location: chr3:180631513 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.23 · 1 PDB

Full CCDC39 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

CCDC39 c.1034+2T>A Pathogenic/Likely pathogenic ★★ same condition
CCDC39 c.1167+1261A>G Pathogenic/Likely pathogenic ★★ same condition
CCDC39 c.1362+1G>A Likely pathogenic ★★ same condition
CCDC39 c.1999-2A>T Pathogenic/Likely pathogenic ★★ same condition
CCDC39 c.210+2T>C Pathogenic ★★ same condition
CCDC39 c.357+1G>C Pathogenic ★★ same condition
CCDC39 c.516+1G>A Likely pathogenic ★★ same condition
CCDC39 c.610-2A>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/ccdc39-p-pro652ser (accessed [today's date]).

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