APC p.Ser2830fs
c.8488dup · rs2533871675 · VCV2773776
ClinGen expert panel — InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
Uncertain Significance for classic or attenuated familial adenomatous polyposis. Applied ACMG criteria (verbatim):
PM2_Supporting
Curation rationale (ClinGen, verbatim)
The NM_000038.6(APC):c.8488dup (p.Ser2830fs*3) variant in APC is a frameshift variant located downstream of codon 2645, therefore PVS1 is not applicable based on the ACMG/AMP criteria specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The variant has been reported in one individual without a colorectal cancer/polyposis associated phenotype not meeting criteria for BS2 (BS2 not met; Ambry internal data). In summary, this variant is a variant of uncertain significance (VUS) for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: criteria PM2_Supporting applied (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 7.7 | GERP 2.6, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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.Ser2830fs
- Coding
- c.8488dup
- MANE Select
- NM_000038
- dbSNP
- rs2533871675
- Type
- Duplication
- Location
- chr5:112844079 (GRCh38)
- Gene constraint
- LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 2830
- the 'interaction with dlg1' region; the 'interaction with mapre1' region; the 'disordered' region
Similar variants
- APC p.Ser2830= Benign/Likely benign ★★ same residue
- APC p.Ser2830Asn Uncertain significance ★ same residue
- APC p.Gln12fs Uncertain significance ★★★ same condition
- APC c.1412dupG Pathogenic ★★ same condition
- APC c.1958+1_1958+2dup Pathogenic/Likely pathogenic ★★ same condition
- APC c.531+2dup Pathogenic ★★ same condition
- APC p.Ala885fs Pathogenic ★★ same condition
- APC p.Ala896fs 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-ser2830fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown