Is ABCC8 c.1817+2T>C pathogenic?

ABCC8 c.1817+2T>C is classified Pathogenic/Likely pathogenic in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-16). Very rare (popmax 8.48e-05%, nfe); Associated with hyperinsulinemic hypoglycemia, familial, 1.

What condition is associated with ABCC8 c.1817+2T>C?

ABCC8 c.1817+2T>C is associated with hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 c.1817+2T>C in the general population?

ABCC8 c.1817+2T>C is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ABCC8 c.1817+2T>C

rs772723050 · VCV2137019

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hyperinsulinemic hypoglycemia, familial, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.88	donor gain · deltas
Pangolin	Δ0.83	loss · gain 0.62 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Non-coding constraint	Z 2.16	1 kb window · o/e 0.86 · regional · uncalibrated
Overall
CADD	35.0	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,924 alleles

Overall 6.84e-05% 1/1,461,760 alleles · very rare

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
Coding: c.1817+2T>C
MANE Select: NM_000352
dbSNP: rs772723050
Type: single nucleotide variant
Location: chr11:17430812 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 8 PDB

Full ABCC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperinsulinemic hypoglycemia, familial, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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.2041-21G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.2116+1G>T 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-c-1817-plus-2t-c (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown