APC2 p.Pro1559=
c.4677G>A · rs369651604 · VCV713385
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.219%, mid)
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 -2 | GERP -1.2 |
| Overall | ||
| CADD | 1.053 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.219%
Middle Eastern · 13/5,942 alleles
Filtering AF
0.129%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.103%
Overall
0.017%
268/1,577,848 alleles · rare
exomes 231/1,425,690 · genomes 37/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.219% | 457 |
| Admixed American | 0.0651% | 1,536 |
| Remaining individualsnot grpmax-eligible | 0.0587% | 1,704 |
| European (non-Finnish) | 0.0149% | 6,732 |
| African / African-American | 0.00975% | 10,259 |
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.Pro1559=
- Coding
- c.4677G>A
- MANE Select
- NM_005883
- dbSNP
- rs369651604
- Type
- single nucleotide variant
- Location
- chr19:1467978 (GRCh38)
- Gene constraint
- LOEUF 0.961 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.87
- Residue 1559
- the '5 x 20 aa approximate repeat of f-x-v-e-x-t-p-x-c-f-s-r-x-s-s-l-s-s-l-s' region; the 'interaction with ctnnb1' region; the 'disordered' region; a UniProt-annotated variant site (in cdcbm10)
Similar variants
- APC2 p.Pro1559Leu 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-pro1559 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown