Is APC p.Ala1316= (c.3948T>C) pathogenic?

APC p.Ala1316= (c.3948T>C) is classified Likely benign in APC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-12). Absent from gnomAD v4.1; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ala1316= (c.3948T>C)?

APC p.Ala1316= (c.3948T>C) is associated with familial adenomatous polyposis 1, hereditary neoplastic syndrome (ClinVar).

How common is APC p.Ala1316= (c.3948T>C) in the general population?

APC p.Ala1316= (c.3948T>C) is absent from gnomAD v4.1 (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.Ala1316=

c.3948T>C · rs943596772 · VCV485130

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -5.9, phastCons 0.001
Overall
CADD	2.052	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.Ala1316=
Coding: c.3948T>C
MANE Select: NM_000038
dbSNP: rs943596772
Type: single nucleotide variant
Location: chr5:112839542 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1316: the 'responsible for down-regulation through a process mediated by direct ubiquitination' region; 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

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.Ala1316Gly Uncertain significance ★ ⚠ same residue
APC p.Ala1316Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
APC p.Ala1316fs Pathogenic ★ 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
APC c.1409-3T>G 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-ala1316 (accessed [today's date]).

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