Is APC p.Ser494fs (c.1477_1478dup) pathogenic?

APC p.Ser494fs (c.14771478dup) is classified Likely pathogenic in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-03). No gnomAD frequency available for this variant; Associated with classic familial adenomatous polyposis.

What condition is associated with APC p.Ser494fs (c.1477_1478dup)?

APC p.Ser494fs (c.1477_1478dup) is associated with classic familial adenomatous polyposis (ClinVar).

How common is APC p.Ser494fs (c.1477_1478dup) in the general population?

APC p.Ser494fs (c.1477_1478dup) 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.Ser494fs

c.1477_1478dup · rs2533197102 · VCV1804874

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

classic familial adenomatous polyposis

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 12 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 2.8, phastCons 1

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.Ser494fs
Coding: c.1477_1478dup
MANE Select: NM_000038
dbSNP: rs2533197102
Type: Duplication
Location: chr5:112827175 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 494: an α-helix

Full APC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

classic familial adenomatous polyposis — 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 c.1958+1_1958+2dup Pathogenic/Likely pathogenic ★★ same condition
APC p.Gly511fs Pathogenic ★★ same condition
APC p.Ile404fs Pathogenic ★★ same condition
APC p.Leu1862fs Pathogenic/Likely pathogenic ★★ same condition
APC p.Lys45fs Pathogenic ★★ same condition
APC p.Ser1658fs Pathogenic/Likely pathogenic ★★ same condition
APC p.Thr1301fs Pathogenic/Likely pathogenic ★★ same condition
APC p.Tyr416fs Pathogenic/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-ser494fs (accessed [today's date]).

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