APC2 p.Ala439=
c.1317C>T · rs34953512 · VCV1667419
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.72%, 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 -14 | GERP -3.5 |
| Overall | ||
| CADD | 3.965 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.72%
Middle Eastern · 225/6,054 alleles
Filtering AF
3.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.5%
Overall
3.12%
50,281/1,613,372 alleles · low-frequency
exomes 46,964/1,461,034 · genomes 3,317/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 3.72% | 27 |
| European (non-Finnish) | 3.54% | 28 |
| South Asian | 3.3% | 30 |
| Remaining individualsnot grpmax-eligible | 3.14% | 32 |
| Ashkenazi Jewishnot grpmax-eligible | 3.11% | 32 |
| Admixed American | 1.72% | 58 |
| Finnishnot grpmax-eligible | 1.46% | 68 |
| African / African-American | 0.532% | 188 |
| Amishnot grpmax-eligible | 0.11% | 912 |
| East Asian | 0.00891% | 11,222 |
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.Ala439=
- Coding
- c.1317C>T
- MANE Select
- NM_005883
- dbSNP
- rs34953512
- Type
- single nucleotide variant
- Location
- chr19:1460194 (GRCh38)
- Gene constraint
- LOEUF 0.961 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.87
- Residue 439
- a UniProt-annotated variant site (in cdcbm10)
Similar variants
- APC2 p.Ala439Val 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-ala439 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown