ABCC8 p.Gly70Glu
c.209G>A · VCV4818241
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9516 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
Hereditary hyperinsulinism
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9516 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.928 | moderately pathogenic-leaning |
| SaProt | LLR -9.99 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.4, phastCons 1 |
| Regional constraint | o/e 0.84 | unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic |
| Overall | ||
| CADD | 27.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ABCC8
- Protein
- p.Gly70Glu
- Coding
- c.209G>A
- MANE Select
- NM_000352
- Type
- single nucleotide variant
- Location
- chr11:17474967 (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 70
- a UniProt-annotated variant site (in hhf1; altered intracellular trafficking)
Disease context
Hereditary hyperinsulinism
Similar variants
- ABCC8 p.Gly70Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same condition
- ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same condition
- ABCC8 c.2116+2T>C Pathogenic/Likely pathogenic ★★ same condition
- ABCC8 c.2117-1G>A Pathogenic ★★ same condition
- ABCC8 c.2475+2T>A Likely pathogenic ★★ same condition
- ABCC8 c.3988+2T>C Pathogenic/Likely pathogenic ★★ same condition
- ABCC8 c.3989-9G>A Pathogenic ★★ same condition
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-gly70glu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown