Is APC p.Ala2128= (c.6384T>G) pathogenic?

APC p.Ala2128= (c.6384T>G) is classified Likely benign in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-01). Absent from gnomAD v4.1; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Ala2128= (c.6384T>G)?

APC p.Ala2128= (c.6384T>G) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ala2128= (c.6384T>G) in the general population?

APC p.Ala2128= (c.6384T>G) 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.Ala2128=

c.6384T>G · rs1580670325 · VCV1080266

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 -0.26	GERP -5.9, phastCons 0.48
Overall
CADD	4.236	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.Ala2128=
Coding: c.6384T>G
MANE Select: NM_000038
dbSNP: rs1580670325
Type: single nucleotide variant
Location: chr5:112841978 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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.Ala2128Gly Uncertain significance ★★ ⚠ same residue
APC p.Ala2128Asp Uncertain significance ★ same residue
APC p.Ala2128Val Conflicting classifications of pathogenicity ★ same residue
APC p.Ala2128fs Pathogenic/Likely 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

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-ala2128 (accessed [today's date]).

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