Is APC p.Arg283Ter (c.847C>T) pathogenic?

APC p.Arg283Ter (c.847C>T) is classified Pathogenic in APC (ClinVar, Expert panel, 17 submitters; last evaluated 2023-02-18). Very rare (popmax 0.00034%, nfe); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Arg283Ter (c.847C>T)?

APC p.Arg283Ter (c.847C>T) is associated with familial adenomatous polyposis 1, gastric cancer, colon carcinoma (ClinVar).

How common is APC p.Arg283Ter (c.847C>T) in the general population?

APC p.Arg283Ter (c.847C>T) is very rare (popmax 0.00034%, nfe) (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.Arg283Ter

c.847C>T · rs786201856 · VCV184999

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 17 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Conditions

familial adenomatous polyposis 1

ClinGen expert panel — InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Pathogenic for familial adenomatous polyposis 1. Applied ACMG criteria (verbatim):

PVS1 PP1_Strong PM2_Supporting PS4_VeryStrong

Curation rationale (ClinGen, verbatim)

The c.847C>T (p.Arg283*) variant in APC is a nonsense variant located between codon 49 and 2645 and predicted to cause a premature stop codon in exon 9 in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been reported in 15 probands meeting 8 phenotype points. In addition, this variant is also reported in 50 probands with FAP not otherwise specified, meeting ≥ 16 phenotype points in total (PS4_VeryStrong; PMIDs 30897307, 20924072, 20685668, 10768871, 9950360, 12901799, 11857735, 26625971, 23159591, Bonn internal data). The variant has been reported to segregate with FAP in 5 meioses from 1 family and in 31 members from 1 large FAP family (PP1_Strong; PMID: 12901799, Bonn internal data). The variant is not reported in gnomAD (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PVS1, PS4_VeryStrong, PM2_Supporting and PP1_Strong (VCEP specifications version 1; date of approval: 12/12/2022).

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 9 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.8, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 4/1,177,804 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,458,666 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APC
Protein: p.Arg283Ter
Coding: c.847C>T
MANE Select: NM_000038
dbSNP: rs786201856
Type: single nucleotide variant
Location: chr5:112815507 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 283: 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: gastric cancer colon carcinoma colorectal cancer hepatocellular carcinoma hereditary neoplastic syndrome gastric adenocarcinoma and proximal polyposis of the stomach classic familial adenomatous polyposis gastric neoplasm

For Familial adenomatous polyposis (Orphanet):

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

Similar variants

APC p.Arg283= Likely benign ★★ same residue
APC p.Arg283Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
APC p.Arg283Gly Uncertain significance ★ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G Pathogenic ★★★ same condition
APC c.1312+5G>A Likely pathogenic ★★★ same condition
APC c.1312+5G>C Likely pathogenic ★★★ same condition
APC c.1409-3T>G 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-arg283ter (accessed [today's date]).

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