Is APC p.Arg141fs (c.421_422del) pathogenic?

APC p.Arg141fs (c.421422del) is classified Pathogenic in APC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-30). Absent from gnomAD; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Arg141fs (c.421_422del)?

APC p.Arg141fs (c.421_422del) is associated with familial adenomatous polyposis 1, hereditary neoplastic syndrome (ClinVar).

How common is APC p.Arg141fs (c.421_422del) in the general population?

APC p.Arg141fs (c.421_422del) is absent from gnomAD (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.Arg141fs

c.421_422del · rs1554069850 · VCV469954

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 4 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APC
Protein: p.Arg141fs
Coding: c.421_422del
MANE Select: NM_000038
dbSNP: rs1554069850
Type: Microsatellite
Location: chr5:112767385 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 141: 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

Also linked: hereditary neoplastic syndrome

For Familial adenomatous polyposis (Orphanet):

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

Similar variants

APC p.Arg141Lys Uncertain significance ★★★ same residue
APC p.Arg141Thr Uncertain significance ★★★ ⚠ same residue
APC p.Arg141Ser Pathogenic ★★ same residue
APC p.Arg141= Uncertain significance ★★ same residue
APC p.Arg141Gly Uncertain significance ★★ ⚠ same residue
APC c.531+5_531+8del Likely pathogenic ★★★ same condition
APC p.Gln2600fs Likely pathogenic ★★★ same condition
APC p.Glu2655fs Uncertain significance ★★★ 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-arg141fs (accessed [today's date]).

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