ABCA2 p.Ser617=
c.1851G>A · VCV4906016
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0186%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.26 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -2.7 |
| Overall | ||
| CADD | 7.625 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0186%
European (non-Finnish) · 218/1,171,180 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0158%
Overall
0.0142%
226/1,588,402 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0186% | 5,372 |
| Remaining individualsnot grpmax-eligible | 0.00649% | 15,413 |
| African / African-American | 0.00435% | 22,981 |
| Admixed American | 0.00174% | 57,536 |
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.Ser617=
- Coding
- c.1851G>A
- MANE Select
- NM_001606
- Type
- single nucleotide variant
- Location
- chr9:137018320 (GRCh38)
- Gene constraint
- LOEUF 0.436 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.46
- Residue 617
- a UniProt-annotated variant site (in idpogsa)
Similar variants
- ABCA2 p.Ser617Leu Uncertain significance ★ ⚠ same residue
- ABCA2 p.Ser617fs Pathogenic ★ 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
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-ser617 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown