Is APC p.Ser295fs (c.883delinsTAC) pathogenic?

APC p.Ser295fs (c.883delinsTAC) is classified Likely pathogenic in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). No gnomAD frequency available for this variant; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ser295fs (c.883delinsTAC)?

APC p.Ser295fs (c.883delinsTAC) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ser295fs (c.883delinsTAC) in the general population?

APC p.Ser295fs (c.883delinsTAC) 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.Ser295fs

c.883delinsTAC · rs2532969068 · VCV3240177

Likely pathogenic Single submitter

Classification

Likely pathogenic

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	predicted	premature termination codon in exon 9 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.14	GERP -5.2, phastCons 0.002

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.Ser295fs
Coding: c.883delinsTAC
MANE Select: NM_000038
dbSNP: rs2532969068
Type: Indel
Location: chr5:112815543 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 295: the 'disordered' 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.Ser295Asn Uncertain significance ★ ⚠ same residue
APC p.Ser295Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
APC p.Ser295Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
APC c.931_933+2delinsCA Pathogenic/Likely pathogenic ★★ same condition
APC c.-192_-191delinsTAGCAAGGG Likely pathogenic ★★ same condition
APC p.Ala1598fs Pathogenic/Likely pathogenic ★★ same condition
APC p.Gly253fs Pathogenic ★★ same condition
APC p.His931fs 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-ser295fs (accessed [today's date]).

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