ABCA12 p.Glu594=
c.1782G>A · rs376960143 · VCV1678769
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.71 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.76 | loss · gain 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 2.4, phastCons 1 |
| Overall | ||
| CADD | 18.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,006 alleles
Overall
6.84e-05%
1/1,461,812 alleles · very rare
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
- ABCA12
- Protein
- p.Glu594=
- Coding
- c.1782G>A
- MANE Select
- NM_173076
- dbSNP
- rs376960143
- Type
- single nucleotide variant
- Location
- chr2:215018008 (GRCh38)
- Gene constraint
- LOEUF 0.582 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.32
- Residue 594
- a UniProt-annotated variant site (in arci4b)
Similar variants
- ABCA12 c.2592+1G>A Likely pathogenic ★★ same type
- ABCA12 c.5381+1G>C Pathogenic/Likely pathogenic ★★ same type
- ABCA12 c.985+1G>A Likely pathogenic ★★ same type
- ABCA12 p.Arg1297Ter Pathogenic ★★ same type
- ABCA12 p.Arg1514Cys Pathogenic ★★ same type
- ABCA12 p.Arg1514His Pathogenic/Likely pathogenic ★★ same type
- ABCA12 p.Arg1515Ter Pathogenic ★★ same type
- ABCA12 p.Arg1950Ter 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/abca12-p-glu594 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown