Is APC p.Ser2349= (c.7047A>G) pathogenic?

APC p.Ser2349= (c.7047A>G) is classified Benign in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). Very rare (popmax 0.00133%, afr); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ser2349= (c.7047A>G)?

APC p.Ser2349= (c.7047A>G) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ser2349= (c.7047A>G) in the general population?

APC p.Ser2349= (c.7047A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Familial adenomatous polyposis inherited?

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

APC p.Ser2349=

c.7047A>G · rs1274342268 · VCV3253914

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -5.1, phastCons 0.85
Overall
CADD	2.891	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,932 alleles

Overall 0.000124% 2/1,613,836 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,932
European (non-Finnish)	8.48e-05%	1,179,866

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.Ser2349=
Coding: c.7047A>G
MANE Select: NM_000038
dbSNP: rs1274342268
Type: single nucleotide variant
Location: chr5:112842641 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2349: 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.Ser2349Leu Uncertain significance ★★ 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
APC c.1626+2T>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-ser2349 (accessed [today's date]).

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