Is APC p.Ser47Ala (c.139T>G) pathogenic?

APC p.Ser47Ala (c.139T>G) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-07). Absent from gnomAD v4.1; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ser47Ala (c.139T>G)?

APC p.Ser47Ala (c.139T>G) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ser47Ala (c.139T>G) in the general population?

APC p.Ser47Ala (c.139T>G) 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.

APC p.Ser47Ala

c.139T>G · rs2149631336 · VCV2819088

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.108	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.64	GERP -2.2, phastCons 0.001
Overall
CADD	12.7	PHRED · no single calibrated threshold — expert panels disagree

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.Ser47Ala
Coding: c.139T>G
MANE Select: NM_000038 · reported on NM_001127511
dbSNP: rs2149631336
Type: single nucleotide variant
Location: chr5:112707856 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 47: an α-helix

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.Val47Leu Uncertain significance ★★ same residue
APC p.Ser47= Uncertain significance ★ same residue
APC p.Ser47Cys Uncertain significance ★ same residue
APC p.Ser47Phe Uncertain significance ★ same residue
APC p.Val47Glu Uncertain significance ★ same residue
APC p.Val47Ile Conflicting classifications of pathogenicity ★ same residue
APC p.Val47= Benign ★ same residue
APC p.Ser47del Uncertain significance ★ same residue

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-ser47ala (accessed [today's date]).

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