Is APC p.Pro2747Arg (c.8240C>G) pathogenic?

APC p.Pro2747Arg (c.8240C>G) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.121); Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Pro2747Arg (c.8240C>G)?

APC p.Pro2747Arg (c.8240C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is APC p.Pro2747Arg (c.8240C>G) in the general population?

APC p.Pro2747Arg (c.8240C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about APC p.Pro2747Arg (c.8240C>G)?

AlphaMissense predicts likely benign (score 0.121) — an in-silico prediction, not a clinical call.

APC p.Pro2747Arg

c.8240C>G · rs774747249 · VCV1762595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.121	likely benign
REVEL	0.236	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 3.3	GERP 1.1, phastCons 0.59
Regional constraint	o/e 1.08	unconstrained · MANE · 4,236 bp · p 0.00065 · regional, not allelic
Overall
CADD	19.34	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,948 alleles

Overall 6.2e-05% 1/1,614,022 alleles · very rare exomes 1/1,461,776 · genomes 0/152,246 · joint denominator

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.Pro2747Arg
Coding: c.8240C>G
MANE Select: NM_000038
dbSNP: rs774747249
Type: single nucleotide variant
Location: chr5:112843834 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2747: 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

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

Similar variants

APC p.Pro2747Ala Uncertain significance ★★ ⚠ same residue
APC p.Pro2747Leu Uncertain significance ★ ⚠ same residue
APC p.Pro2747Ser Uncertain significance ★ ⚠ same residue
APC p.Pro2747= 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

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-pro2747arg (accessed [today's date]).

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