ABCC8 p.Phe536=
c.1608T>C · rs753618932 · VCV1620412
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, 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 -3.8 | GERP -4.9 |
| Overall | ||
| CADD | 0.726 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
South Asian · 10/91,046 alleles
Filtering AF
0.00594%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00453%
Overall
0.000744%
12/1,613,796 alleles · ultra-rare
exomes 12/1,461,530 · genomes 0/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.011% | 9,105 |
| East Asian | 0.00223% | 44,872 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
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.Phe536=
- Coding
- c.1608T>C
- MANE Select
- NM_000352
- dbSNP
- rs753618932
- Type
- single nucleotide variant
- Location
- chr11:17442742 (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 536
- an α-helix; the abc transmembrane type-1 1 domain
Similar variants
- ABCC8 p.Phe536Leu Likely pathogenic ★ ⚠ 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-phe536 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown