APC2 p.Glu396=
c.1188G>A · rs1291942983 · VCV2883694
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00601%, amr)
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 -0.12 | GERP -0.34, phastCons 0.001 |
| Overall | ||
| CADD | 0.931 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00601%
Admixed American · 3/49,904 alleles
Filtering AF
0.0016%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000842%
Overall
0.00065%
9/1,385,632 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00601% | 16,635 |
| African / African-American | 0.00277% | 36,050 |
| East Asian | 0.00249% | 40,102 |
| South Asian | 0.0024% | 41,606 |
| European (non-Finnish) | 8.73e-05% | 1,145,265 |
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.Glu396=
- Coding
- c.1188G>A
- MANE Select
- NM_005883
- dbSNP
- rs1291942983
- Type
- single nucleotide variant
- Location
- chr19:1457224 (GRCh38)
- Gene constraint
- LOEUF 0.961 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.87
- Residue 396
- a UniProt-annotated variant site (in cdcbm10)
Similar variants
- APC2 p.Glu396Lys 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
- APC2 p.Ala1438Thr 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-glu396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown