Is CCDC39 p.Lys190fs (c.570_571del) pathogenic?

CCDC39 p.Lys190fs (c.570571del) is classified Pathogenic/Likely pathogenic in CCDC39 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-26). Very rare (popmax 0.000424%, nfe); Associated with CCDC39-related disorder.

What condition is associated with CCDC39 p.Lys190fs (c.570_571del)?

CCDC39 p.Lys190fs (c.570_571del) is associated with CCDC39-related disorder, primary ciliary dyskinesia (ClinVar).

How common is CCDC39 p.Lys190fs (c.570_571del) in the general population?

CCDC39 p.Lys190fs (c.570_571del) is very rare (popmax 0.000424%, nfe) (gnomAD).

CCDC39 p.Lys190fs

c.570_571del · rs1560092160 · VCV572863

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

CCDC39-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP -0.7, phastCons 0.17
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,386 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,612,588 alleles · very rare

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.Lys190fs
Coding: c.570_571del
MANE Select: NM_181426
dbSNP: rs1560092160
Type: Deletion
Location: chr3:180659715 (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

CCDC39-related disorder

Also linked: primary ciliary dyskinesia

Similar variants

CCDC39 p.Lys190Asn Uncertain significance ★ ⚠ same residue
CCDC39 p.Lys190= Likely benign ★ same residue
CCDC39 c.610_613del Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Arg542fs Pathogenic ★★ same condition
CCDC39 p.Arg615_Tyr616insTer Pathogenic/Likely pathogenic ★★ same condition
CCDC39 p.Cys680fs Pathogenic ★★ same condition
CCDC39 p.Cys73fs Pathogenic ★★ same condition
CCDC39 p.Gln833fs 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/ccdc39-p-lys190fs (accessed [today's date]).

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