Is APC p.Arg405Ter (c.1213C>T) pathogenic?

APC p.Arg405Ter (c.1213C>T) is classified Pathogenic in APC (ClinVar, Multiple submitters, 19 submitters; last evaluated 2025-12-17). Very rare (popmax 0.00134%, afr); Associated with Inherited polyposis and early onset colorectal cancer - germline testing.

What condition is associated with APC p.Arg405Ter (c.1213C>T)?

APC p.Arg405Ter (c.1213C>T) is associated with Inherited polyposis and early onset colorectal cancer - germline testing, hereditary neoplastic syndrome, classic familial adenomatous polyposis (ClinVar).

How common is APC p.Arg405Ter (c.1213C>T) in the general population?

APC p.Arg405Ter (c.1213C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

APC p.Arg405Ter

c.1213C>T · rs587779780 · VCV127275

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Inherited polyposis and early onset colorectal cancer - germline testing

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 10 of 16
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Overall
CADD	45.0	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 0.00134% African / African-American · 1/74,906 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,778 alleles · very rare exomes 5/1,461,634 · genomes 1/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,906
European (non-Finnish)	0.000424%	235,989

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.Arg405Ter
Coding: c.1213C>T
MANE Select: NM_000038
dbSNP: rs587779780
Type: single nucleotide variant
Location: chr5:112819245 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

Inherited polyposis and early onset colorectal cancer - germline testing

Also linked: hereditary neoplastic syndrome classic familial adenomatous polyposis familial adenomatous polyposis 1

Similar variants

APC p.Arg405Gln Uncertain significance ★★ same residue
APC p.Arg405Pro Uncertain significance ★ same residue
APC p.Arg405= Likely benign ★ same residue
APC p.Arg405fs Pathogenic ★ same residue
APC p.Arg405Gly 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-arg405ter (accessed [today's date]).

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