Is APC p.Ser130fs (c.388dup) pathogenic?

APC p.Ser130fs (c.388dup) is classified Pathogenic/Likely pathogenic in APC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-08). Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ser130fs (c.388dup)?

APC p.Ser130fs (c.388dup) is associated with familial adenomatous polyposis 1 (ClinVar).

How is Familial adenomatous polyposis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

APC p.Ser130fs

c.388dup · VCV3658063

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	phastCons 1

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

Variant & gene context

Gene: APC
Protein: p.Ser130fs
Coding: c.388dup
MANE Select: NM_000038
Type: Duplication
Location: chr5:112767353 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

familial adenomatous polyposis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial adenomatous polyposis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

APC p.Ser130Cys Uncertain significance ★★ same residue
APC p.Ser130Ile Uncertain significance ★★ same residue
APC p.Ser130= Benign/Likely benign ★★ same residue
APC p.Ser130Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
APC p.Ser634fs Pathogenic ★★★ same condition
APC p.Gln12fs Uncertain significance ★★★ same condition
APC c.1412dupG Pathogenic ★★ same condition
APC c.531+2dup 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/apc-p-ser130fs (accessed [today's date]).

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