Is CCDC78 p.Arg231Gln (c.692G>A) pathogenic?

CCDC78 p.Arg231Gln (c.692G>A) is classified Likely benign in CCDC78 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-03). AlphaMissense: likely benign (0.0756); Rare (popmax 0.115%, afr); Associated with congenital myopathy with internal nuclei and atypical cores.

What condition is associated with CCDC78 p.Arg231Gln (c.692G>A)?

CCDC78 p.Arg231Gln (c.692G>A) is associated with congenital myopathy with internal nuclei and atypical cores (ClinVar).

How common is CCDC78 p.Arg231Gln (c.692G>A) in the general population?

CCDC78 p.Arg231Gln (c.692G>A) is rare (popmax 0.115%, afr) (gnomAD).

What do computational predictors say about CCDC78 p.Arg231Gln (c.692G>A)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

CCDC78 p.Arg231Gln

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.692G>A · rs147504073 · VCV473263

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myopathy with internal nuclei and atypical cores

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -4.6
Regional constraint	o/e 1.20	unconstrained · MANE · 3,686 bp · p 9.6e-07 · regional, not allelic
Overall
CADD	0.198	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 0.115% African / African-American · 86/75,052 alleles

Filtering AF 0.095% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0878%

Overall 0.0085% 137/1,612,066 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.115%	873
Middle Eastern	0.033%	3,029
East Asian	0.0201%	4,985
Remaining individualsnot grpmax-eligible	0.00961%	10,405
Admixed American	0.005%	19,981
European (non-Finnish)	0.00246%	40,681
South Asian	0.0022%	45,456

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.Arg231Gln
Coding: c.692G>A
MANE Select: NM_001378030
dbSNP: rs147504073
Type: single nucleotide variant
Location: chr16:724754 (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.Arg231Trp Uncertain significance ★★ ⚠ same residue
CCDC78 p.Arg231Gly Uncertain significance ★ ⚠ same residue
CCDC78 p.Arg231Leu Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg231gln (accessed [today's date]).

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