Is CCDC78 p.Ala172= (c.516G>A) pathogenic?

CCDC78 p.Ala172= (c.516G>A) is classified Likely benign in CCDC78 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). Very rare (popmax 0.0011%, sas); Associated with congenital myopathy with internal nuclei and atypical cores.

What condition is associated with CCDC78 p.Ala172= (c.516G>A)?

CCDC78 p.Ala172= (c.516G>A) is associated with congenital myopathy with internal nuclei and atypical cores (ClinVar).

How common is CCDC78 p.Ala172= (c.516G>A) in the general population?

CCDC78 p.Ala172= (c.516G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

CCDC78 p.Ala172=

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.516G>A · VCV4763509

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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	0.002	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.8	GERP -3.7
Overall
CADD	2.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,088 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000753% 11/1,460,460 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,088
European (non-Finnish)	0.000847%	117,999

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.Ala172=
Coding: c.516G>A
MANE Select: NM_001378030
Type: single nucleotide variant
Location: chr16:725122 (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.Ala172Val Uncertain significance ★ ⚠ same residue
CCDC78 p.Ala172Thr 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

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-ala172 (accessed [today's date]).

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