Is CCDC78 p.Arg16fs (c.41_44dup) pathogenic?

CCDC78 p.Arg16fs (c.4144dup) is classified Uncertain significance in CCDC78 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). Very rare (popmax 0.00686%, afr); Associated with congenital myopathy with internal nuclei and atypical cores.

What condition is associated with CCDC78 p.Arg16fs (c.41_44dup)?

CCDC78 p.Arg16fs (c.41_44dup) is associated with congenital myopathy with internal nuclei and atypical cores (ClinVar).

How common is CCDC78 p.Arg16fs (c.41_44dup) in the general population?

CCDC78 p.Arg16fs (c.41_44dup) is very rare (popmax 0.00686%, afr) (gnomAD).

CCDC78 p.Arg16fs

Q: How is Congenital myopathy with internal nuclei and atypical cores inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.41_44dup · VCV4699314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00686%, afr)

Conditions

congenital myopathy with internal nuclei and atypical cores

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 1 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.052	GERP -2.3
Overall
CADD	20.4	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 0.00686% African / African-American · 5/72,900 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.000323% 5/1,548,276 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: CCDC78
Protein: p.Arg16fs
Coding: c.41_44dup
MANE Select: NM_001378030
Type: Microsatellite
Location: chr16:726323 (GRCh38)
Gene constraint: LOEUF 1.615 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.65

Full CCDC78 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myopathy with internal nuclei and atypical cores — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital myopathy with internal nuclei and atypical cores (Orphanet):

Inheritance: Autosomal dominant
Onset: Neonatal

Similar variants

CCDC78 p.Arg16Gly Uncertain significance ★★ ⚠ same residue
CCDC78 p.Arg16Pro Uncertain significance ★ ⚠ same residue
CCDC78 p.Arg16Trp Uncertain significance ★ ⚠ same residue
CCDC78 p.Arg16Gln Likely benign ★ same residue
CCDC78 c.560_560+3del Uncertain significance ★ same condition
CCDC78 p.His142fs Uncertain significance ★ same condition
CCDC78 p.Leu102_Arg103insGluLeu Uncertain significance ★ same condition
CCDC78 p.Lys170fs Uncertain significance ★ 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/ccdc78-p-arg16fs (accessed [today's date]).

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