Is APC p.Ser47Phe (c.140C>T) pathogenic?

APC p.Ser47Phe (c.140C>T) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-02). Very rare (popmax 0.00143%, afr); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ser47Phe (c.140C>T)?

APC p.Ser47Phe (c.140C>T) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ser47Phe (c.140C>T) in the general population?

APC p.Ser47Phe (c.140C>T) is very rare (popmax 0.00143%, 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.Ser47Phe

c.140C>T · rs1750615769 · VCV1433650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00143%, afr)

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.18	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.87, phastCons 0.86
Overall
CADD	15.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00143% African / African-American · 1/69,852 alleles

Overall 0.000146% 2/1,370,110 alleles · very rare exomes 2/1,217,826 · genomes 0/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00143%	69,852
European (non-Finnish)	9.63e-05%	1,038,540

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.Ser47Phe
Coding: c.140C>T
MANE Select: NM_000038 · reported on NM_001127511
dbSNP: rs1750615769
Type: single nucleotide variant
Location: chr5:112707857 (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.Ser47Ala Uncertain significance ★ same residue
APC p.Ser47Cys 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-ser47phe (accessed [today's date]).

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