Is CCDC78 p.Tyr243= (c.729C>T) pathogenic?

CCDC78 p.Tyr243= (c.729C>T) is classified Likely benign in CCDC78 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). Ultra-rare (popmax 0.01%, amr); Associated with congenital myopathy with internal nuclei and atypical cores.

What condition is associated with CCDC78 p.Tyr243= (c.729C>T)?

CCDC78 p.Tyr243= (c.729C>T) is associated with congenital myopathy with internal nuclei and atypical cores (ClinVar).

How common is CCDC78 p.Tyr243= (c.729C>T) in the general population?

CCDC78 p.Tyr243= (c.729C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

CCDC78 p.Tyr243=

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.729C>T · rs376412009 · VCV1099331

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

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	0.08	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.3	GERP -4.6
Overall
CADD	0.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,968 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.0013% 21/1,611,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,995
African / African-American	0.00934%	10,702
South Asian	0.0055%	18,197
Remaining individualsnot grpmax-eligible	0.0016%	62,428
European (non-Finnish)	0.00017%	589,890

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.Tyr243=
Coding: c.729C>T
MANE Select: NM_001378030
dbSNP: rs376412009
Type: single nucleotide variant
Location: chr16:724717 (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.Tyr243Ter 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-tyr243 (accessed [today's date]).

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