Is CCDC78 p.Thr7Ile (c.20C>T) pathogenic?

CCDC78 p.Thr7Ile (c.20C>T) is classified Uncertain significance in CCDC78 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). AlphaMissense: likely benign (0.2289); Very rare (popmax 0.00553%, afr); Associated with Inborn genetic diseases.

What condition is associated with CCDC78 p.Thr7Ile (c.20C>T)?

CCDC78 p.Thr7Ile (c.20C>T) is associated with Inborn genetic diseases, congenital myopathy with internal nuclei and atypical cores (ClinVar).

How common is CCDC78 p.Thr7Ile (c.20C>T) in the general population?

CCDC78 p.Thr7Ile (c.20C>T) is very rare (popmax 0.00553%, afr) (gnomAD).

What do computational predictors say about CCDC78 p.Thr7Ile (c.20C>T)?

AlphaMissense predicts likely benign (score 0.2289) — an in-silico prediction, not a clinical call.

CCDC78 p.Thr7Ile

c.20C>T · rs868059787 · VCV2065647

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00553%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2289	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -8.24	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 2	GERP -2.2, phastCons 0.016
Regional constraint	o/e 1.20	unconstrained · MANE · 3,686 bp · p 9.6e-07 · regional, not allelic
Overall
CADD	18.39	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00553% African / African-American · 4/72,382 alleles

Filtering AF 0.00179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.000324% 5/1,542,960 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00553%	18,095
European (non-Finnish)	8.73e-05%	1,145,814

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.Thr7Ile
Coding: c.20C>T
MANE Select: NM_001378030
dbSNP: rs868059787
Type: single nucleotide variant
Location: chr16:726348 (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 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-thr7ile (accessed [today's date]).

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