Is APC p.Pro14fs (c.40_49del) pathogenic?

APC p.Pro14fs (c.4049del) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). No gnomAD frequency available for this variant; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Pro14fs (c.40_49del)?

APC p.Pro14fs (c.40_49del) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Pro14fs (c.40_49del) in the general population?

APC p.Pro14fs (c.40_49del) is no gnomAD frequency available for this variant (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.Pro14fs

c.40_49del · rs2149630638 · VCV1052820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.9	GERP -3.9

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APC
Protein: p.Pro14fs
Coding: c.40_49del
MANE Select: NM_000038 · reported on NM_001127511
dbSNP: rs2149630638
Type: Deletion
Location: chr5:112707755 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 14: 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.Glu14= Likely benign ★★ same residue
APC p.Glu14Val Uncertain significance ★ same residue
APC p.Pro14= Uncertain significance ★ same residue
APC p.Pro14Ala Uncertain significance ★ same residue
APC p.Pro14Leu Uncertain significance ★ same residue
APC p.Pro14Ser Uncertain significance ★ same residue
APC c.1311_1312+1del Pathogenic ★★★ same condition
APC c.1312+4_1312+19del 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-pro14fs (accessed [today's date]).

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