APC2 p.Ala595=
c.1785C>T · rs537258047 · VCV2039455
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0333%, 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 -3 | GERP -3.5 |
| Overall | ||
| CADD | 7.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0333%
Admixed American · 20/60,008 alleles
Filtering AF
0.0221%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0184%
Overall
0.00136%
22/1,612,896 alleles · ultra-rare
exomes 16/1,460,610 · genomes 6/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0333% | 3,000 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,496 |
| South Asian | 0.0011% | 91,086 |
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.Ala595=
- Coding
- c.1785C>T
- MANE Select
- NM_005883
- dbSNP
- rs537258047
- Type
- single nucleotide variant
- Location
- chr19:1462109 (GRCh38)
- Gene constraint
- LOEUF 0.961 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.87
- Residue 595
- a UniProt-annotated variant site (in cdcbm10)
Similar variants
- APC2 p.Ala595Val 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-ala595 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown