ABCA1 p.Ser954=
c.2862G>A · VCV3339316
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0467%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.38 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.20 | gain · loss 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -5 | GERP -4.2 |
| Overall | ||
| CADD | 13.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0467%
Admixed American · 28/60,000 alleles
Filtering AF
0.0331%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0286%
Overall
0.00204%
33/1,613,900 alleles · ultra-rare
exomes 31/1,461,742 · genomes 2/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0467% | 2,143 |
| Middle Eastern | 0.0167% | 5,984 |
| Finnishnot grpmax-eligible | 0.00312% | 32,014 |
| African / African-American | 0.00133% | 74,916 |
| South Asian | 0.0011% | 91,080 |
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
- ABCA1
- Protein
- p.Ser954=
- Coding
- c.2862G>A
- MANE Select
- NM_005502
- Type
- single nucleotide variant
- Location
- chr9:104821473 (GRCh38)
- Gene constraint
- LOEUF 0.563 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.50 · 7 PDB
- Residue 954
- the abc transporter 1 domain; a β-strand
Similar variants
- ABCA1 p.Ser954Leu Uncertain significance ★★ ⚠ same residue
- ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same type
- ABCA1 c.4274+1G>A Likely pathogenic ★★ same type
- ABCA1 c.5237+3A>C Likely pathogenic ★★ same type
- ABCA1 p.Arg2080Trp Likely pathogenic ★★ same type
- ABCA1 p.Arg557Ter Pathogenic/Likely pathogenic ★★ same type
- ABCA1 p.Arg587Trp Pathogenic/Likely pathogenic ★★ same type
- ABCA1 p.Asn1800His Pathogenic/Likely pathogenic ★★ ⚠ 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/abca1-p-ser954 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown