Is CCDC39 p.Glu272Asp (c.816G>T) pathogenic?

CCDC39 p.Glu272Asp (c.816G>T) is classified Uncertain significance in CCDC39 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-18). AlphaMissense: likely pathogenic (0.8907); Very rare (popmax 0.004%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Glu272Asp (c.816G>T)?

CCDC39 p.Glu272Asp (c.816G>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC39 p.Glu272Asp (c.816G>T) in the general population?

CCDC39 p.Glu272Asp (c.816G>T) is very rare (popmax 0.004%, nfe) (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.Glu272Asp (c.816G>T)?

AlphaMissense predicts likely pathogenic (score 0.8907) — an in-silico prediction, not a clinical call.

CCDC39 p.Glu272Asp

c.816G>T · rs775659100 · VCV944494

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.8907	likely pathogenic · top 3% in CCDC39
REVEL	0.433	indeterminate
SaProt	LLR -8.21	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP -1.4, phastCons 0.64
Regional constraint	o/e 0.99	unconstrained · MANE · 64 kb · p 0.72 · regional, not allelic
Overall
CADD	20.8	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 0.004% European (non-Finnish) · 47/1,173,976 alleles

Filtering AF 0.00308% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00277%

Overall 0.00294% 47/1,596,820 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.Glu272Asp
Coding: c.816G>T
MANE Select: NM_181426
dbSNP: rs775659100
Type: single nucleotide variant
Location: chr3:180654876 (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

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.Glu272= 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-glu272asp (accessed [today's date]).

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