APC2 p.Ala466=
c.1398G>A · rs763564005 · VCV2981772
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0312%, 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 -20 | GERP -3.5 |
| Overall | ||
| CADD | 0.364 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0312%
East Asian · 14/44,900 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.00527%
85/1,613,424 alleles · ultra-rare
exomes 81/1,461,170 · genomes 4/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0312% | 3,207 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,869 |
| South Asian | 0.00768% | 13,013 |
| Admixed American | 0.00667% | 15,002 |
| European (non-Finnish) | 0.00432% | 23,138 |
| African / African-American | 0.004% | 24,986 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
| Finnishnot grpmax-eligible | 0.00158% | 63,366 |
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.Ala466=
- Coding
- c.1398G>A
- MANE Select
- NM_005883
- dbSNP
- rs763564005
- Type
- single nucleotide variant
- Location
- chr19:1460275 (GRCh38)
- Gene constraint
- LOEUF 0.961 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.87
- Residue 466
- a UniProt-annotated variant site (in cdcbm10)
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-ala466 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown