Is APC2 p.Cys313fs (c.935dup) pathogenic?

APC2 p.Cys313fs (c.935dup) is classified Likely pathogenic in APC2 (ClinVar, Single submitter, 1 submitter). Associated with cortical dysplasia, complex, with other brain malformations 10.

What condition is associated with APC2 p.Cys313fs (c.935dup)?

APC2 p.Cys313fs (c.935dup) is associated with cortical dysplasia, complex, with other brain malformations 10, intellectual developmental disorder, autosomal recessive 74 (ClinVar).

APC2 p.Cys313fs

c.935dup · VCV4796569

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

cortical dysplasia, complex, with other brain malformations 10

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 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: APC2
Protein: p.Cys313fs
Coding: c.935dup
MANE Select: NM_005883
Type: Duplication
Location: chr19:1456968 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 313: a UniProt-annotated variant site (in cdcbm10)

Full APC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cortical dysplasia, complex, with other brain malformations 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual developmental disorder, autosomal recessive 74

Similar variants

APC2 p.Gln267fs Likely pathogenic ★ same condition
APC2 p.Glu254fs Likely pathogenic ★ same condition
APC2 p.Ser552fs Pathogenic ★ same condition
APC2 p.Ala841_Lys842insAlaAla Uncertain significance ★ same condition
APC2 p.Lys1734fs Pathogenic same condition
APC2 p.Ala1703Glu Uncertain significance ★★ ⚠ same condition
APC2 p.Ala791Val Uncertain significance ★★ ⚠ same condition
APC2 p.Arg1081Gly 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/apc2-p-cys313fs (accessed [today's date]).

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