APC p.Ser2601fs
c.7803_7807del · rs1580686729 · VCV648862
ClinGen expert panel — InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
Likely Pathogenic for familial adenomatous polyposis 1. Applied ACMG criteria (verbatim):
PVS1 PM2_Supporting
Curation rationale (ClinGen, verbatim)
The NM_000038.6(APC):c.7803_7807del (p.Ser2601ArgfsTer17) variant in APC is a frameshift variant located between codon 49 and 2645 and predicted to cause a premature stop codon in exon 16 in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been reported in 1 proband with a colorectal cancer/polyposis associated phenotype not meeting phenotypic criteria (PS4 not met; internal data Labcorp Genetics [formerly Invitae]). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP: PVS1 and PM2_Supporting (VCEP specifications version v2.1.0; date of approval 11/24/2023).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 | 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 · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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.Ser2601fs
- Coding
- c.7803_7807del
- MANE Select
- NM_000038
- dbSNP
- rs1580686729
- Type
- Deletion
- Location
- chr5:112843393 (GRCh38)
- Gene constraint
- LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 2601
- the 'disordered' region; the 'basic region' region; the 'interaction with dlg1' region
Disease context
familial adenomatous polyposis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso 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.Ser2601Arg Uncertain significance ★★ ⚠ same residue
- APC p.Ser2601Asn Uncertain significance ★★ ⚠ same residue
- APC p.Ser2601Thr Uncertain significance ★ ⚠ same residue
- APC p.Ser2601= Likely benign ★ same residue
- APC c.1311_1312+1del Pathogenic ★★★ same condition
- APC c.1312+4_1312+19del Likely pathogenic ★★★ same condition
- APC p.Glu2172fs Pathogenic ★★★ same condition
- APC p.Gly53fs 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-ser2601fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown