Is APC p.Arg1069fs (c.3206_3213del) pathogenic?

APC p.Arg1069fs (c.32063213del) is classified Pathogenic in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). No gnomAD frequency available for this variant; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Arg1069fs (c.3206_3213del)?

APC p.Arg1069fs (c.3206_3213del) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Arg1069fs (c.3206_3213del) in the general population?

APC p.Arg1069fs (c.3206_3213del) 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.Arg1069fs

c.3206_3213del · rs2533479247 · VCV2584008

Pathogenic Single submitter

Classification

Pathogenic

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	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 0.54	GERP 2.7, phastCons 0.98

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.Arg1069fs
Coding: c.3206_3213del
MANE Select: NM_000038
dbSNP: rs2533479247
Type: Deletion
Location: chr5:112838794 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1069: the 'responsible for down-regulation through a process mediated by direct ubiquitination' region; the 'interaction with catenins' 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

For Familial adenomatous polyposis (Orphanet):

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

Similar variants

APC p.Arg1069Met Uncertain significance ★★ same residue
APC p.Arg1069Ser Uncertain significance ★★ same residue
APC p.Arg1069= Likely benign ★★ same residue
APC p.Arg1069Gly Conflicting classifications of pathogenicity ★ same residue
APC p.Arg1069Thr Uncertain significance ★ same residue
APC c.1311_1312+1del Pathogenic ★★★ same condition
APC c.1312+4_1312+19del Likely pathogenic ★★★ same condition
APC p.Glu2172fs 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-arg1069fs (accessed [today's date]).

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