Is CCDC39 p.Leu158Val (c.472C>G) pathogenic?

CCDC39 p.Leu158Val (c.472C>G) is classified Benign/Likely benign in CCDC39 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0691); Common (popmax 13.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Leu158Val (c.472C>G)?

CCDC39 p.Leu158Val (c.472C>G) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 14 (ClinVar).

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.Leu158Val (c.472C>G)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

CCDC39 p.Leu158Val

Q: How common is CCDC39 p.Leu158Val (c.472C>G) in the general population?

CCDC39 p.Leu158Val (c.472C>G) is common (popmax 13.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.472C>G · rs57838737 · VCV226485

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 13.5%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.46	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 0.85	GERP -1.1, phastCons 0.18
Regional constraint	o/e 0.99	unconstrained · MANE · 64 kb · p 0.72 · regional, not allelic
Overall
CADD	6.266	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 13.5% African / African-American · 10,060/74,790 alleles

Filtering AF 13.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.1%

Overall 0.736% 11,782/1,601,418 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.5%	7
Remaining individualsnot grpmax-eligible	0.952%	105
Admixed American	0.88%	114
Middle Eastern	0.761%	131
Ashkenazi Jewishnot grpmax-eligible	0.236%	424
European (non-Finnish)	0.0403%	2,480
South Asian	0.0304%	3,293
Finnishnot grpmax-eligible	0.00315%	31,713

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.Leu158Val
Coding: c.472C>G
MANE Select: NM_181426
dbSNP: rs57838737
Type: single nucleotide variant
Location: chr3:180660614 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia 14

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

CCDC39 p.Leu158= Likely benign ★★ same residue
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

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-leu158val (accessed [today's date]).

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