# NM_000352.4:c.(?_1818)_(1923_?)del

https://sugi.bio/variant/abcc8-c-1818

## Summary

**ABCC8 c.(?_1818** is classified **Pathogenic** in ABCC8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-05-01). Associated with hyperinsulinemic hypoglycemia, familial, 1.

**At a glance:** Pathogenic · review: No assertion criteria · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the ABCC8 gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to hyperinsulinemic hypoglycemia, familial, 1.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0024690/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [ABCC8](https://sugi.bio/atlas/gene/ABCC8/) |
| Coding change (HGVS c.) | c.(?_1818 |
| MANE Select transcript | [NM_000352](https://www.ncbi.nlm.nih.gov/nuccore/NM_000352) |
| Variant type | Deletion |
| ClinVar | [VCV39470](https://www.ncbi.nlm.nih.gov/clinvar/variation/39470/) |

## Gene constraint & dosage {#gene-context}

**ABCC8** population constraint: LOEUF 0.829, pLI 9.5344e-33, missense-Z 2.8451; ClinGen dosage — haploinsufficiency gene assoc. with recessive phenotype, triplosensitivity 0/3. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **pulmonary arterial hypertension** — Moderate (AD)
- **hyperinsulinism** — Definitive (AD)
- **hyperinsulinemic hypoglycemia, familial, 1** — Definitive (AR)
- **monogenic diabetes** — Definitive (SD)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 82.56, 42% of residues very-high.

**8 experimental structure(s)** (PDB): [6C3O](https://www.rcsb.org/structure/6C3O), [6C3P](https://www.rcsb.org/structure/6C3P), [7S5V](https://www.rcsb.org/structure/7S5V), [7S5X](https://www.rcsb.org/structure/7S5X), [7S5Y](https://www.rcsb.org/structure/7S5Y), [7S5Z](https://www.rcsb.org/structure/7S5Z).

## What this gene does {#gene-function}

*Describes the biological roles of ABCC8 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** ABCC8's established molecular role includes potassium channel activity. In Reactome, ABCC8 is annotated in disease pathway(s) including **Defective ABCC8 can cause hypo- and hyper-glycemias**.

**Disease mechanism (Reactome):** ABCC8 loss or alteration is curated in [Defective ABCC8 can cause hypo- and hyper-glycemias](https://reactome.org/content/detail/R-HSA-5683177).

### Pathways affected {#pathways}

ABCC8 participates in **3 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Defective ABCC8 can cause hypo- and hyper-glycemias](https://reactome.org/content/detail/R-HSA-5683177) | curated |
| [ATP sensitive Potassium channels](https://reactome.org/content/detail/R-HSA-1296025) | curated |
| [Regulation of insulin secretion](https://reactome.org/content/detail/R-HSA-422356) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** potassium channel activity, ATPase-coupled monoatomic cation transmembrane transporter activity, transmembrane transporter binding.

## Clinical significance {#significance}

**Pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2012-05-01.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| OMIM | Pathogenic | no assertion criteria provided | literature only | 2012-05-01 |

## Associated conditions {#conditions}

[hyperinsulinemic hypoglycemia, familial, 1](https://sugi.bio/atlas/disease/hyperinsulinemic-hypoglycemia-familial-1/).

**Reported phenotype names (ClinVar):** Hyperinsulinemic hypoglycemia, familial, 1, Persistent hyperinsulinemic hypoglycemia of infancy, HYPERINSULINISM, FAMILIAL, WITH PANCREATIC NESIDIOBLASTOSIS, HYPOGLYCEMIA, HYPERINSULINEMIC, OF INFANCY, NESIDIOBLASTOSIS OF PANCREAS, Persistent Hyperinsulinemia Hypoglycemia of Infancy.

## Similar variants {#similar}

Related ABCC8 variant pages (same residue, condition, or type): [ABCC8 p.Ala269fs](/variant/abcc8-p-ala269fs), [ABCC8 p.Gln632fs](/variant/abcc8-p-gln632fs), [ABCC8 p.His627fs](/variant/abcc8-p-his627fs), [ABCC8 p.Ile450fs](/variant/abcc8-p-ile450fs), [ABCC8 p.Ile550fs](/variant/abcc8-p-ile550fs), [ABCC8 p.Leu1170fs](/variant/abcc8-p-leu1170fs), [ABCC8 p.Leu178_Tyr179insTer](/variant/abcc8-p-leu178-tyr179inster), [ABCC8 p.Phe1387del](/variant/abcc8-p-phe1387del).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 39470). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*