Is ABCC8 p.Ile89fs (c.267del) pathogenic?

ABCC8 p.Ile89fs (c.267del) is classified Likely pathogenic in ABCC8 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with hyperinsulinemic hypoglycemia, familial, 1.

What condition is associated with ABCC8 p.Ile89fs (c.267del)?

ABCC8 p.Ile89fs (c.267del) is associated with hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 p.Ile89fs (c.267del) in the general population?

ABCC8 p.Ile89fs (c.267del) is absent from gnomAD (gnomAD).

ABCC8 p.Ile89fs

c.267del · rs2133728449 · VCV1526016

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hyperinsulinemic hypoglycemia, familial, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	GERP 1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCC8
Protein: p.Ile89fs
Coding: c.267del
MANE Select: NM_000352
dbSNP: rs2133728449
Type: Deletion
Location: chr11:17474909 (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 89: an α-helix

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 p.Ala269fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Gln632fs Pathogenic ★★ same condition
ABCC8 p.His627fs Pathogenic ★★ same condition
ABCC8 p.Ile450fs Pathogenic ★★ same condition
ABCC8 p.Ile550fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Leu1170fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Leu178_Tyr179insTer Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Phe1387del 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-ile89fs (accessed [today's date]).

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