Is APC p.Ala2800Pro (c.8398G>C) pathogenic?

APC p.Ala2800Pro (c.8398G>C) is classified Uncertain significance in APC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-29). AlphaMissense: likely benign (0.0964); Ultra-rare (popmax 0.0336%, mid); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ala2800Pro (c.8398G>C)?

APC p.Ala2800Pro (c.8398G>C) is associated with familial adenomatous polyposis 1, hereditary neoplastic syndrome (ClinVar).

How common is APC p.Ala2800Pro (c.8398G>C) in the general population?

APC p.Ala2800Pro (c.8398G>C) is ultra-rare (popmax 0.0336%, mid) (gnomAD).

How is Familial adenomatous polyposis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about APC p.Ala2800Pro (c.8398G>C)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

APC p.Ala2800Pro

c.8398G>C · rs1554089100 · VCV957199

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0336%, mid)

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.332	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.86, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,236 bp · p 0.00065 · regional, not allelic
Overall
CADD	18.15	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0336% Middle Eastern · 2/5,956 alleles

Filtering AF 0.00591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.000138% 2/1,448,894 alleles · ultra-rare

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.Ala2800Pro
Coding: c.8398G>C
MANE Select: NM_000038
dbSNP: rs1554089100
Type: single nucleotide variant
Location: chr5:112843992 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2800: the 'interaction with dlg1' region; the 'interaction with mapre1' region; the 'disordered' region

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.Ala2800Ser Uncertain significance ★★ ⚠ same residue
APC p.Ala2800= Benign/Likely benign ★★ same residue
APC p.Ala2800Asp Uncertain significance ★ same residue
APC p.Ala2800Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala2800pro (accessed [today's date]).

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