ABCA1 p.Ser2249=
c.6747T>C · rs375203349 · VCV1655975
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00788%, nfe)
Conditions
1
Cardiovascular phenotype
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 2.4 | GERP 0.92, phastCons 1 |
| Overall | ||
| CADD | 7.374 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00788%
European (non-Finnish) · 93/1,180,002 alleles
Filtering AF
0.00656%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00608%
Overall
0.00595%
96/1,613,980 alleles · very rare
exomes 92/1,461,796 · genomes 4/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00788% | 12,688 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| African / African-American | 0.00133% | 74,918 |
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.Ser2249=
- Coding
- c.6747T>C
- MANE Select
- NM_005502
- dbSNP
- rs375203349
- Type
- single nucleotide variant
- Location
- chr9:104784354 (GRCh38)
- Gene constraint
- LOEUF 0.563 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.50 · 7 PDB
Similar variants
- ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ABCA1 p.Thr940Met Pathogenic/Likely pathogenic ★★ same condition
- ABCA1 c.3787+5C>A Uncertain significance ★★ same condition
- ABCA1 p.Ala1855Ser Uncertain significance ★★ ⚠ same condition
- ABCA1 p.Ala766Ser Uncertain significance ★★ ⚠ same condition
- ABCA1 p.Arg1283Cys Uncertain significance ★★ ⚠ same condition
- ABCA1 p.Arg1342Trp Uncertain significance ★★ ⚠ same condition
- ABCA1 p.Arg1417Cys Uncertain significance ★★ ⚠ same condition
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-ser2249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown