Is APC p.Ala1305= (c.3915A>G) pathogenic?

APC p.Ala1305= (c.3915A>G) is classified Conflicting classifications of pathogenicity in APC (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-05-19). Absent from gnomAD v4.1; Associated with classic or attenuated familial adenomatous polyposis.

What condition is associated with APC p.Ala1305= (c.3915A>G)?

APC p.Ala1305= (c.3915A>G) is associated with classic or attenuated familial adenomatous polyposis, hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ala1305= (c.3915A>G) in the general population?

APC p.Ala1305= (c.3915A>G) is absent from gnomAD v4.1 (gnomAD).

APC p.Ala1305=

c.3915A>G · rs2149901988 · VCV2072479

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

classic or attenuated familial adenomatous polyposis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -3.3, phastCons 0.63
Overall
CADD	3.789	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APC
Protein: p.Ala1305=
Coding: c.3915A>G
MANE Select: NM_000038
dbSNP: rs2149901988
Type: single nucleotide variant
Location: chr5:112839509 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1305: the 'responsible for down-regulation through a process mediated by direct ubiquitination' region

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

Disease context

classic or attenuated familial adenomatous polyposis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome familial adenomatous polyposis 1

Similar variants

APC p.Ala1305Thr Uncertain significance ★★ ⚠ same residue
APC p.Ala1305Gly Uncertain significance ★ ⚠ same residue
APC p.Ala1305Val Uncertain significance ★ ⚠ same residue
APC p.Ala1305del Uncertain significance ★ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G Pathogenic ★★★ same condition
APC c.1312+5G>A Likely pathogenic ★★★ same condition
APC c.1312+5G>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-ala1305 (accessed [today's date]).

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