Is APC p.Ala1283= (c.3849T>C) pathogenic?

APC p.Ala1283= (c.3849T>C) is classified Likely benign in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-30). Very rare (popmax 8.48e-05%, nfe); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ala1283= (c.3849T>C)?

APC p.Ala1283= (c.3849T>C) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ala1283= (c.3849T>C) in the general population?

APC p.Ala1283= (c.3849T>C) is very rare (popmax 8.48e-05%, nfe) (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.Ala1283=

c.3849T>C · rs2149900377 · VCV1149336

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 0.014	GERP -3.4, phastCons 0.95
Overall
CADD	5.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,894 alleles

Overall 6.2e-05% 1/1,614,048 alleles · very rare exomes 1/1,461,726 · genomes 0/152,322 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APC
Protein: p.Ala1283=
Coding: c.3849T>C
MANE Select: NM_000038
dbSNP: rs2149900377
Type: single nucleotide variant
Location: chr5:112839443 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1283: 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

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.Ala1283Pro Uncertain significance ★★ same residue
APC p.Ala1283Thr Uncertain significance ★★ same residue
APC p.Ala1283Val Uncertain significance ★ same residue
APC p.Ala1283Ser 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-ala1283 (accessed [today's date]).

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