Is APC p.Glu658Met (c.1972_1973delinsAT) pathogenic?

APC p.Glu658Met (c.19721973delinsAT) is classified Uncertain significance in APC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-30). No gnomAD frequency available for this variant; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Glu658Met (c.1972_1973delinsAT)?

APC p.Glu658Met (c.1972_1973delinsAT) is associated with familial adenomatous polyposis 1, hereditary neoplastic syndrome (ClinVar).

How common is APC p.Glu658Met (c.1972_1973delinsAT) in the general population?

APC p.Glu658Met (c.1972_1973delinsAT) 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.Glu658Met

c.1972_1973delinsAT · rs1765077325 · VCV853601

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 4.8e-05 · regional, not allelic

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.Glu658Met
Coding: c.1972_1973delinsAT
MANE Select: NM_000038
dbSNP: rs1765077325
Type: Indel
Location: chr5:112837566 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 658: 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: hereditary neoplastic syndrome

For Familial adenomatous polyposis (Orphanet):

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

Similar variants

APC p.Glu658fs Pathogenic ★★ same residue
APC p.Glu658Gln Uncertain significance ★★ same residue
APC p.Glu658Lys Uncertain significance ★★ same residue
APC p.Glu658Val Uncertain significance ★★ same residue
APC p.Glu658= Benign/Likely benign ★★ same residue
APC p.Glu658_Asn659insLys Uncertain significance ★ same residue
APC p.Glu658Gly Uncertain significance ★ same residue
APC c.931_933+2delinsCA 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-glu658met (accessed [today's date]).

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