Is APC p.Ser1970fs (c.5906dup) pathogenic?

APC p.Ser1970fs (c.5906dup) is classified Pathogenic/Likely pathogenic in APC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-02). Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ser1970fs (c.5906dup)?

APC p.Ser1970fs (c.5906dup) is associated with familial adenomatous polyposis 1, hereditary neoplastic syndrome (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.Ser1970fs

c.5906dup · VCV4725724

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	escapes	premature termination codon in the last exon (16 of 16) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP -0.69, phastCons 1

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

Variant & gene context

Gene: APC
Protein: p.Ser1970fs
Coding: c.5906dup
MANE Select: NM_000038
Type: Duplication
Location: chr5:112841499 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1970: the 'disordered' region

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

Also linked: hereditary neoplastic syndrome

For Familial adenomatous polyposis (Orphanet):

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

Similar variants

APC p.Ser1970Arg Uncertain significance ★★ ⚠ same residue
APC p.Ser1970Asn Uncertain significance ★★ same residue
APC p.Ser1970Gly Uncertain significance ★★ ⚠ same residue
APC p.Ser1970Ile Uncertain significance ★★ ⚠ same residue
APC p.Ser1970Cys Uncertain significance ★ ⚠ same residue
APC p.Ser1970Thr Uncertain significance ★ ⚠ same residue
APC p.Ser634fs Pathogenic ★★★ same condition
APC p.Gln12fs 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/apc-p-ser1970fs (accessed [today's date]).

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