Is CC2D1A p.Asp321fs (c.959dup) pathogenic?

CC2D1A p.Asp321fs (c.959dup) is classified Likely pathogenic in CC2D1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). Associated with intellectual disability, autosomal recessive 3.

What condition is associated with CC2D1A p.Asp321fs (c.959dup)?

CC2D1A p.Asp321fs (c.959dup) is associated with intellectual disability, autosomal recessive 3 (ClinVar).

CC2D1A p.Asp321fs

c.959dup · VCV3376456

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual disability, autosomal recessive 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -2.6, phastCons 0.44

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

Variant & gene context

Gene: CC2D1A
Protein: p.Asp321fs
Coding: c.959dup
MANE Select: NM_017721
Type: Duplication
Location: chr19:13918753 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB
Residue 321: the 'disordered' region

Full CC2D1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal recessive 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CC2D1A p.Arg355fs Pathogenic/Likely pathogenic ★★ same condition
CC2D1A p.Asp321= Likely benign ★★ same residue
CC2D1A p.Lys374fs Likely pathogenic ★ same condition
CC2D1A p.Pro542fs Likely pathogenic ★ same condition
CC2D1A p.7_9PPG[3] Conflicting classifications of pathogenicity ★ same condition
CC2D1A p.Asp321Glu Uncertain significance ★ ⚠ same residue
CC2D1A c.2225+1G>A Likely pathogenic ★★ same condition
CC2D1A c.2454+1G>A Likely pathogenic ★★ 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/cc2d1a-p-asp321fs (accessed [today's date]).

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