ABCC8 p.Lys649Ter
c.1945A>T · rs2496668620 · VCV1726667
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
hyperinsulinemic hypoglycemia, familial, 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 14 of 39 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 42.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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.Lys649Ter
- Coding
- c.1945A>T
- MANE Select
- NM_000352
- dbSNP
- rs2496668620
- Type
- single nucleotide variant
- Location
- chr11:17428384 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.56 · 8 PDB
Similar variants
- ABCC8 p.Lys649= 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.148+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCC8 c.148+2T>G Likely pathogenic ★★ same condition
- ABCC8 c.1630+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCC8 c.1630+1G>T Pathogenic ★★ same condition
- ABCC8 c.1817+2T>C Pathogenic/Likely 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-lys649ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown