ABCA2 p.Tyr462=
c.1386C>T · VCV4821146
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.508%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.348 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.70 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -4.5 | GERP -2.2 |
| Overall | ||
| CADD | 1.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.508%
African / African-American · 381/75,054 alleles
Filtering AF
0.466%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.449%
Overall
0.028%
452/1,613,068 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.508% | 197 |
| Remaining individualsnot grpmax-eligible | 0.0304% | 3,288 |
| Admixed American | 0.0267% | 3,752 |
| European (non-Finnish) | 0.00297% | 33,714 |
| South Asian | 0.0011% | 91,088 |
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.Tyr462=
- Coding
- c.1386C>T
- MANE Select
- NM_001606
- Type
- single nucleotide variant
- Location
- chr9:137020375 (GRCh38)
- Gene constraint
- LOEUF 0.436 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.46
- Residue 462
- a UniProt-annotated variant site (in idpogsa)
Similar variants
- 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
- ABCA2 p.Ala2206Val 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-tyr462 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown