Is APC p.Arg374fs (c.1121_1143del) pathogenic?

APC p.Arg374fs (c.11211143del) is classified Pathogenic in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Arg374fs (c.1121_1143del)?

APC p.Arg374fs (c.1121_1143del) 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.Arg374fs

c.1121_1143del · VCV4071405

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 10 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1

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

Variant & gene context

Gene: APC
Protein: p.Arg374fs
Coding: c.1121_1143del
MANE Select: NM_000038
Type: Deletion
Location: chr5:112819151 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 374: 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.Arg374Pro Uncertain significance ★★ same residue
APC p.Arg374Trp Uncertain significance ★★ ⚠ same residue
APC p.Arg374= Conflicting classifications of pathogenicity ★ same residue
APC p.Arg374Gln Conflicting classifications of pathogenicity ★ 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
APC p.Gly53fs Likely 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-arg374fs (accessed [today's date]).

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