Is CCDC78 p.Glu128Asp (c.384G>T) pathogenic?

CCDC78 p.Glu128Asp (c.384G>T) is classified Conflicting classifications of pathogenicity in CCDC78 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.1481); Rare (popmax 0.566%, afr); Associated with Inborn genetic diseases.

What condition is associated with CCDC78 p.Glu128Asp (c.384G>T)?

CCDC78 p.Glu128Asp (c.384G>T) is associated with Inborn genetic diseases, congenital myopathy with internal nuclei and atypical cores (ClinVar).

How common is CCDC78 p.Glu128Asp (c.384G>T) in the general population?

CCDC78 p.Glu128Asp (c.384G>T) is rare (popmax 0.566%, afr) (gnomAD).

What do computational predictors say about CCDC78 p.Glu128Asp (c.384G>T)?

AlphaMissense predicts likely benign (score 0.1481) — an in-silico prediction, not a clinical call.

CCDC78 p.Glu128Asp

c.384G>T · rs145274257 · VCV447008

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1481 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.566%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1481	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -6.30	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 -0.24	GERP -4
Regional constraint	o/e 1.20	unconstrained · MANE · 3,686 bp · p 9.6e-07 · regional, not allelic
Overall
CADD	4.595	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 0.566% African / African-American · 425/75,066 alleles

Filtering AF 0.522% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.504%

Overall 0.0321% 518/1,612,778 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.566%	177
Admixed American	0.0783%	1,277
Remaining individualsnot grpmax-eligible	0.0432%	2,314
East Asian	0.00223%	44,882
European (non-Finnish)	0.00153%	65,554

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.Glu128Asp
Coding: c.384G>T
MANE Select: NM_001378030
dbSNP: rs145274257
Type: single nucleotide variant
Location: chr16:725464 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myopathy with internal nuclei and atypical cores

Similar variants

CCDC78 p.Glu128= Likely benign ★ 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-glu128asp (accessed [today's date]).

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