Is CCDC78 p.Pro340= (c.1020C>T) pathogenic?

CCDC78 p.Pro340= (c.1020C>T) is classified Likely benign in CCDC78 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-09). Ultra-rare (popmax 0.0166%, mid); Associated with congenital myopathy with internal nuclei and atypical cores.

What condition is associated with CCDC78 p.Pro340= (c.1020C>T)?

CCDC78 p.Pro340= (c.1020C>T) is associated with congenital myopathy with internal nuclei and atypical cores (ClinVar).

How common is CCDC78 p.Pro340= (c.1020C>T) in the general population?

CCDC78 p.Pro340= (c.1020C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

CCDC78 p.Pro340=

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.1020C>T · rs1319236751 · VCV1540116

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

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.
REVEL	0.012	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.13	GERP -3.1
Overall
CADD	1.396	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,008 alleles

Overall 0.000187% 3/1,603,546 alleles · ultra-rare exomes 3/1,451,230 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,008
South Asian	0.00111%	89,720
European (non-Finnish)	8.51e-05%	1,175,320

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.Pro340=
Coding: c.1020C>T
MANE Select: NM_001378030
dbSNP: rs1319236751
Type: single nucleotide variant
Location: chr16:724139 (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.Pro340Leu Uncertain significance ★ ⚠ same residue
CCDC78 c.1053+1G>A Uncertain significance ★★ same condition
CCDC78 c.268-3C>T Uncertain significance ★★ same condition
CCDC78 c.61-1G>A Uncertain significance ★★ same condition
CCDC78 c.61-6C>A Uncertain significance ★★ same condition
CCDC78 c.953+1G>A Uncertain significance ★★ same condition
CCDC78 p.Ala126Val Uncertain significance ★★ ⚠ same condition
CCDC78 p.Ala188Ser 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-pro340 (accessed [today's date]).

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