Is APC p.Ser2310Pro (c.6928T>C) pathogenic?

APC p.Ser2310Pro (c.6928T>C) is classified Uncertain significance in APC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-15). AlphaMissense: ambiguous (0.5051); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Ser2310Pro (c.6928T>C)?

APC p.Ser2310Pro (c.6928T>C) is associated with hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ser2310Pro (c.6928T>C) in the general population?

APC p.Ser2310Pro (c.6928T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APC p.Ser2310Pro (c.6928T>C)?

AlphaMissense predicts ambiguous (score 0.5051) — an in-silico prediction, not a clinical call.

APC p.Ser2310Pro

c.6928T>C · rs1766334843 · VCV845641

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5051 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5051	ambiguous
REVEL	0.449	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,236 bp · p 0.00065 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

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.Ser2310Pro
Coding: c.6928T>C
MANE Select: NM_000038
dbSNP: rs1766334843
Type: single nucleotide variant
Location: chr5:112842522 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2310: the 'disordered' region; the 'basic region' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial adenomatous polyposis 1

Similar variants

APC p.Ser2310Leu Uncertain significance ★★ same residue
APC p.Ser2310= 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-ser2310pro (accessed [today's date]).

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