ABCA2 p.Ala1226=
c.3678C>T · rs373638582 · VCV3025271
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.05%, sas)
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 -7.9 | GERP -3.3 |
| Overall | ||
| CADD | 0.231 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.05%
South Asian · 904/86,036 alleles
Filtering AF
0.994%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.971%
Overall
0.0649%
1,016/1,565,350 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.05% | 95 |
| Remaining individualsnot grpmax-eligible | 0.0693% | 1,444 |
| Middle Eastern | 0.0404% | 2,473 |
| East Asian | 0.0264% | 3,791 |
| Admixed American | 0.00575% | 17,401 |
| African / African-American | 0.00543% | 18,424 |
| European (non-Finnish) | 0.00432% | 23,152 |
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
- ABCA2
- Protein
- p.Ala1226=
- Coding
- c.3678C>T
- MANE Select
- NM_001606
- dbSNP
- rs373638582
- Type
- single nucleotide variant
- Location
- chr9:137015433 (GRCh38)
- Gene constraint
- LOEUF 0.436 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.46
- Residue 1226
- the 'disordered' region; a UniProt-annotated variant site (in idpogsa)
Similar variants
- ABCA2 p.Ala1226Thr Uncertain significance ★ ⚠ same residue
- ABCA2 p.Gln1370Ter Likely pathogenic ★★ same type
- ABCA2 c.3883-3C>T Uncertain significance ★★ same type
- ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same type
- ABCA2 p.Ala1620Thr Uncertain significance ★★ ⚠ same type
- ABCA2 p.Ala1645Val Uncertain significance ★★ ⚠ same type
- ABCA2 p.Ala1715Ser Uncertain significance ★★ ⚠ same type
- ABCA2 p.Ala2180Thr 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/abca2-p-ala1226 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown