Is APC p.Ser2290Pro (c.6868T>C) pathogenic?

APC p.Ser2290Pro (c.6868T>C) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-21). AlphaMissense: likely benign (0.1061); Absent from gnomAD v4.1; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ser2290Pro (c.6868T>C)?

APC p.Ser2290Pro (c.6868T>C) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ser2290Pro (c.6868T>C) in the general population?

APC p.Ser2290Pro (c.6868T>C) is absent from gnomAD v4.1 (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.Ser2290Pro (c.6868T>C)?

AlphaMissense predicts likely benign (score 0.1061) — an in-silico prediction, not a clinical call.

APC p.Ser2290Pro

c.6868T>C · rs2149975076 · VCV2128752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1061 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
AlphaMissense	0.1061	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.2, phastCons 0.92
Regional constraint	o/e 1.08	unconstrained · MANE · 4,236 bp · p 0.00065 · regional, not allelic
Overall
CADD	16.67	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APC
Protein: p.Ser2290Pro
Coding: c.6868T>C
MANE Select: NM_000038
dbSNP: rs2149975076
Type: single nucleotide variant
Location: chr5:112842462 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2290: the 'disordered' region; the 'basic region' 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

For Familial adenomatous polyposis (Orphanet):

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

Similar variants

APC p.Ser2290Phe Uncertain significance ★★ ⚠ same residue
APC p.Ser2290= Benign ★ 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
APC c.1409-3T>G Likely pathogenic ★★★ same condition
APC c.1409-5A>G 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-ser2290pro (accessed [today's date]).

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