Is CCDC78 p.Pro323= (c.969C>A) pathogenic?

CCDC78 p.Pro323= (c.969C>A) is classified Likely benign in CCDC78 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). Absent from gnomAD v4.1; Associated with congenital myopathy with internal nuclei and atypical cores.

What condition is associated with CCDC78 p.Pro323= (c.969C>A)?

CCDC78 p.Pro323= (c.969C>A) is associated with congenital myopathy with internal nuclei and atypical cores (ClinVar).

How common is CCDC78 p.Pro323= (c.969C>A) in the general population?

CCDC78 p.Pro323= (c.969C>A) is absent from gnomAD v4.1 (gnomAD).

CCDC78 p.Pro323=

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.969C>A · rs2151551775 · VCV1084144

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital myopathy with internal nuclei and atypical cores

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.032	moderately benign-leaning
Splicing
SpliceAI	Δ0.46	acceptor gain · deltas
Pangolin	Δ0.29	gain · loss 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.3	GERP -0.93, phastCons 1
Overall
CADD	14.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC78
Protein: p.Pro323=
Coding: c.969C>A
MANE Select: NM_001378030
dbSNP: rs2151551775
Type: single nucleotide variant
Location: chr16:724190 (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 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
CCDC78 p.Ala227Val 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-pro323 (accessed [today's date]).

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