Is APC2 p.Ala2048= (c.6144G>A) pathogenic?

APC2 p.Ala2048= (c.6144G>A) is classified Likely benign in APC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). Very rare (popmax 0.00127%, nfe).

How common is APC2 p.Ala2048= (c.6144G>A) in the general population?

APC2 p.Ala2048= (c.6144G>A) is very rare (popmax 0.00127%, nfe) (gnomAD).

APC2 p.Ala2048=

c.6144G>A · VCV4781846

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

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 -3.4	GERP -1.8
Overall
CADD	0.956	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 12/943,798 alleles

Filtering AF 0.000678% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000535%

Overall 0.00104% 12/1,158,630 alleles · very rare

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.Ala2048=
Coding: c.6144G>A
MANE Select: NM_005883
Type: single nucleotide variant
Location: chr19:1469445 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 2048: 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.Ala2048Glu Uncertain significance ★ ⚠ same residue
APC2 p.Ala2048Val Uncertain significance ★ ⚠ same residue
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

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-ala2048 (accessed [today's date]).

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