ABCC8 p.Ala1453=
c.4359C>T · rs769435360 · VCV1134831
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0192%, sas)
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 0.87 | GERP -5.5, phastCons 1 |
| Overall | ||
| CADD | 7.684 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0192%
South Asian · 17/88,314 alleles
Filtering AF
0.0122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.01%
Overall
0.00125%
20/1,598,900 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0192% | 5,195 |
| African / African-American | 0.00401% | 24,913 |
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
- ABCC8
- Protein
- p.Ala1453=
- Coding
- c.4359C>T
- MANE Select
- NM_000352
- dbSNP
- rs769435360
- Type
- single nucleotide variant
- Location
- chr11:17395224 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.56 · 8 PDB
- Residue 1453
- an α-helix; the abc transporter 2 domain
Similar variants
- ABCC8 p.Ala1453Thr Uncertain significance ★★ ⚠ same residue
- ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same type
- ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same type
- ABCC8 c.148+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCC8 c.148+2T>G Likely pathogenic ★★ same type
- ABCC8 c.1630+1G>A Pathogenic/Likely pathogenic ★★ same type
- ABCC8 c.1630+1G>T Pathogenic ★★ same type
- ABCC8 c.1817+1G>C 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/abcc8-p-ala1453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown