Is APC p.Ser20fs (c.57dup) pathogenic?

APC p.Ser20fs (c.57dup) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-03). No gnomAD frequency available for this variant; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ser20fs (c.57dup)?

APC p.Ser20fs (c.57dup) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ser20fs (c.57dup) in the general population?

APC p.Ser20fs (c.57dup) is no gnomAD frequency available for this variant (gnomAD).

How is Familial adenomatous polyposis inherited?

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

APC p.Ser20fs

c.57dup · rs2149630736 · VCV1055861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.09	GERP -3.9, phastCons 0.004

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: APC
Protein: p.Ser20fs
Coding: c.57dup
MANE Select: NM_000038 · reported on NM_001127511
dbSNP: rs2149630736
Type: Duplication
Location: chr5:112707771 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 20: an α-helix

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.Asn20Thr Uncertain significance ★★ same residue
APC p.Asn20= Conflicting classifications of pathogenicity ★ same residue
APC p.Ser20= Uncertain significance ★ same residue
APC p.Ser20Ter Uncertain significance ★ 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-ser20fs (accessed [today's date]).

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