Is APC2 p.Ala2189= (c.6567C>T) pathogenic?

APC2 p.Ala2189= (c.6567C>T) is classified Likely benign in APC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). Ultra-rare (popmax 0.0382%, eas).

How common is APC2 p.Ala2189= (c.6567C>T) in the general population?

APC2 p.Ala2189= (c.6567C>T) is ultra-rare (popmax 0.0382%, eas) (gnomAD).

APC2 p.Ala2189=

c.6567C>T · rs375186427 · VCV727031

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0382%, eas)

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 -12	GERP -1.9
Overall
CADD	0.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0382% East Asian · 15/39,244 alleles

Filtering AF 0.0235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.019%

Overall 0.00296% 45/1,522,626 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0382%	2,616
Remaining individualsnot grpmax-eligible	0.032%	3,123
Admixed American	0.002%	49,890
South Asian	0.0012%	83,302
European (non-Finnish)	0.000788%	126,891

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: APC2
Protein: p.Ala2189=
Coding: c.6567C>T
MANE Select: NM_005883
dbSNP: rs375186427
Type: single nucleotide variant
Location: chr19:1469868 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 2189: the 'disordered' region; a UniProt-annotated variant site (in cdcbm10)

Full APC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APC2 p.Ala1059Glu Uncertain significance ★★ ⚠ same type
APC2 p.Ala1103Thr Uncertain significance ★★ ⚠ same type
APC2 p.Ala1116Val Uncertain significance ★★ ⚠ same type
APC2 p.Ala126Ser Uncertain significance ★★ ⚠ same type
APC2 p.Ala1311Thr Uncertain significance ★★ ⚠ same type
APC2 p.Ala1359Val Uncertain significance ★★ ⚠ same type
APC2 p.Ala1438Thr Uncertain significance ★★ ⚠ same type
APC2 p.Ala1492Glu Uncertain significance ★★ ⚠ same type

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/apc2-p-ala2189 (accessed [today's date]).

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