Is APC p.Gln161Ter (c.481C>T) pathogenic?

APC p.Gln161Ter (c.481C>T) is classified Pathogenic in APC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-05). Absent from gnomAD v4.1; Associated with classic or attenuated familial adenomatous polyposis.

What condition is associated with APC p.Gln161Ter (c.481C>T)?

APC p.Gln161Ter (c.481C>T) is associated with classic or attenuated familial adenomatous polyposis, hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Gln161Ter (c.481C>T) in the general population?

APC p.Gln161Ter (c.481C>T) is absent from gnomAD v4.1 (gnomAD).

APC p.Gln161Ter

c.481C>T · rs876658325 · VCV229997

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

classic or attenuated familial adenomatous polyposis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 16
Splicing
SpliceAI	Δ0.39	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Overall
CADD	39.0	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.Gln161Ter
Coding: c.481C>T
MANE Select: NM_000038
dbSNP: rs876658325
Type: single nucleotide variant
Location: chr5:112775687 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 161: an α-helix

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

Disease context

classic or attenuated familial adenomatous polyposis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome familial adenomatous polyposis 1

Similar variants

APC p.Gln161Glu Uncertain significance ★★ same residue
APC p.Gln161= Benign/Likely benign ★★ same residue
APC p.Gln161His Uncertain significance ★ same residue
APC p.Gln161Pro 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

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-gln161ter (accessed [today's date]).

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