Is CCDC8 p.Lys29Ter (c.84dup) pathogenic?

CCDC8 p.Lys29Ter (c.84dup) is classified Pathogenic in CCDC8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2011-07-15). Absent from gnomAD; Associated with 3M syndrome 3.

What condition is associated with CCDC8 p.Lys29Ter (c.84dup)?

CCDC8 p.Lys29Ter (c.84dup) is associated with 3M syndrome 3 (ClinVar).

How common is CCDC8 p.Lys29Ter (c.84dup) in the general population?

CCDC8 p.Lys29Ter (c.84dup) is absent from gnomAD (gnomAD).

CCDC8 p.Lys29Ter

c.84dup · rs1568590155 · VCV31105

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

3M syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCDC8
Protein: p.Lys29Ter
Coding: c.84dup
MANE Select: NM_032040
dbSNP: rs1568590155
Type: Duplication
Location: chr19:46412726 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 46.83 · 1 PDB

Full CCDC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

3M syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCDC8 p.Lys29delinsAsnTer Likely pathogenic ★ same residue
CCDC8 p.Lys205fs Likely pathogenic ★ same condition
CCDC8 p.Val8fs Conflicting classifications of pathogenicity ★ same condition
CCDC8 p.Gln327fs Pathogenic/Likely pathogenic ★★ same condition
CCDC8 p.Asp365Ala Uncertain significance ★★ ⚠ same condition
CCDC8 p.Glu337_Arg344del Uncertain significance ★★ same condition
CCDC8 p.Thr96Arg Uncertain significance ★★ ⚠ same condition
CCDC8 p.Ala349Pro Benign/Likely benign ★★ ⚠ 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/ccdc8-p-lys29ter (accessed [today's date]).

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