Is APC p.Ser24Phe (c.71C>T) pathogenic?

APC p.Ser24Phe (c.71C>T) is classified Conflicting classifications of pathogenicity in APC (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0576%, mid); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ser24Phe (c.71C>T)?

APC p.Ser24Phe (c.71C>T) is associated with familial adenomatous polyposis 1, gastric cancer, colorectal cancer (ClinVar).

How common is APC p.Ser24Phe (c.71C>T) in the general population?

APC p.Ser24Phe (c.71C>T) is ultra-rare (popmax 0.0576%, mid) (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.Ser24Phe

c.71C>T · rs770241997 · VCV371851

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0576%, mid)

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.153	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP 0.12, phastCons 1
Overall
CADD	13.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0576% Middle Eastern · 3/5,210 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00834%

Overall 0.00285% 39/1,370,544 alleles · ultra-rare exomes 35/1,218,368 · genomes 4/152,176 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0576%	1,737
Remaining individualsnot grpmax-eligible	0.00397%	25,194
European (non-Finnish)	0.00327%	30,553

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.Ser24Phe
Coding: c.71C>T
MANE Select: NM_000038 · reported on NM_001127511
dbSNP: rs770241997
Type: single nucleotide variant
Location: chr5:112707788 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 24: 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

Also linked: gastric cancer colorectal cancer hepatocellular carcinoma gastric adenocarcinoma and proximal polyposis of the stomach

For Familial adenomatous polyposis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

APC p.Arg24Ter Uncertain significance ★★★ same residue
APC p.Arg24Gln Uncertain significance ★★ same residue
APC p.Arg24Leu Uncertain significance ★★ same residue
APC p.Ser24Cys Uncertain significance ★★ same residue
APC p.Ser24= Uncertain significance ★ same residue
APC p.Arg24Pro Uncertain significance ★ same residue
APC p.Arg24= Likely benign ★ same residue
APC c.1312+3A>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-ser24phe (accessed [today's date]).

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