Is APC p.Arg1114Ter (c.3340C>T) pathogenic?

APC p.Arg1114Ter (c.3340C>T) is classified Pathogenic in APC (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-05-29). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Arg1114Ter (c.3340C>T)?

APC p.Arg1114Ter (c.3340C>T) is associated with hereditary neoplastic syndrome, colon carcinoma, classic familial adenomatous polyposis (ClinVar).

How common is APC p.Arg1114Ter (c.3340C>T) in the general population?

APC p.Arg1114Ter (c.3340C>T) is absent from gnomAD v4.1 (gnomAD).

APC p.Arg1114Ter

c.3340C>T · rs121913331 · VCV236589

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP 1.9, phastCons 1
Overall
CADD	36.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APC
Protein: p.Arg1114Ter
Coding: c.3340C>T
MANE Select: NM_000038
dbSNP: rs121913331
Type: single nucleotide variant
Location: chr5:112838934 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1114: the 'responsible for down-regulation through a process mediated by direct ubiquitination' region; the 'interaction with catenins' 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: colon carcinoma classic familial adenomatous polyposis familial adenomatous polyposis 1

Similar variants

APC p.Arg1114Leu Uncertain significance ★★ same residue
APC p.Arg1114Gln Conflicting classifications of pathogenicity ★ same residue
APC p.Arg1114Gly Uncertain significance ★ same residue
APC p.Arg1114= Likely benign ★ 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

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-arg1114ter (accessed [today's date]).

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