ABCC6 p.Ile746=
c.2238T>C · rs748098140 · VCV1651535
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
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 -7.5 | GERP -3.7 |
| Overall | ||
| CADD | 0.042 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,988 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.00041%
6/1,461,660 alleles · ultra-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
- ABCC6
- Protein
- p.Ile746=
- Coding
- c.2238T>C
- MANE Select
- NM_001171
- dbSNP
- rs748098140
- Type
- single nucleotide variant
- Location
- chr16:16182421 (GRCh38)
- Gene constraint
- LOEUF 0.917 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.32 · 4 PDB
- Residue 746
- a β-strand; the abc transporter 1 domain
Similar variants
- ABCC6 p.Ile746Thr Uncertain significance ★★ ⚠ same residue
- ABCC6 p.Ile746Phe Uncertain significance ★ ⚠ same residue
- ABCC6 p.Ile746Val Uncertain significance ★ ⚠ same residue
- ABCC6 p.Ile746fs Likely pathogenic ★★ same residue
- ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same type
- ABCC6 c.2071-1G>A Likely pathogenic ★★ same type
- ABCC6 c.2591-1G>T Likely pathogenic ★★ same type
- ABCC6 c.2787+1G>T 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/abcc6-p-ile746 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown