APC2 p.Ala1548=
c.4644C>T · rs12980869 · VCV751872
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0354%, 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 -1.1 | GERP -1.2 |
| Overall | ||
| CADD | 4.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0354%
Admixed American · 21/59,340 alleles
Filtering AF
0.0237%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0199%
Overall
0.00139%
22/1,586,838 alleles · ultra-rare
exomes 19/1,434,636 · genomes 3/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0354% | 2,826 |
| South Asian | 0.00112% | 89,674 |
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.Ala1548=
- Coding
- c.4644C>T
- MANE Select
- NM_005883
- dbSNP
- rs12980869
- Type
- single nucleotide variant
- Location
- chr19:1467945 (GRCh38)
- Gene constraint
- LOEUF 0.961 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 48.87
- Residue 1548
- 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.Ala1548Val 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-ala1548 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown