Is APC p.Arg2833= (c.8499C>G) pathogenic?

APC p.Arg2833= (c.8499C>G) is classified Benign/Likely benign in APC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-18). Very rare (popmax 0.00187%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Arg2833= (c.8499C>G)?

APC p.Arg2833= (c.8499C>G) is associated with hereditary neoplastic syndrome, familial adenomatous polyposis 1, classic or attenuated familial adenomatous polyposis (ClinVar).

How common is APC p.Arg2833= (c.8499C>G) in the general population?

APC p.Arg2833= (c.8499C>G) is very rare (popmax 0.00187%, nfe) (gnomAD).

APC p.Arg2833=

c.8499C>G · rs757921527 · VCV232290

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -2, phastCons 0.099
Overall
CADD	3.738	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00187% European (non-Finnish) · 22/1,179,424 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,611,722 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.Arg2833=
Coding: c.8499C>G
MANE Select: NM_000038
dbSNP: rs757921527
Type: single nucleotide variant
Location: chr5:112844093 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2833: the 'interaction with dlg1' region; the 'interaction with mapre1' region; the 'disordered' region

Full APC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial adenomatous polyposis 1 classic or attenuated familial adenomatous polyposis

Similar variants

APC p.Arg2833Gly Uncertain significance ★★ same residue
APC p.Arg2833His Uncertain significance ★★ same residue
APC p.Arg2833Leu Uncertain significance ★★ same residue
APC p.Arg2833Pro Uncertain significance ★ same residue
APC p.Arg2833Cys 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

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-arg2833 (accessed [today's date]).

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