Is ABCC8 p.Asp1408fs (c.4220_4221insACAGG) pathogenic?

ABCC8 p.Asp1408fs (c.42204221insACAGG) is classified Likely pathogenic in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-02). Absent from gnomAD; Associated with hyperinsulinemic hypoglycemia, familial, 1.

What condition is associated with ABCC8 p.Asp1408fs (c.4220_4221insACAGG)?

ABCC8 p.Asp1408fs (c.4220_4221insACAGG) is associated with hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 p.Asp1408fs (c.4220_4221insACAGG) in the general population?

ABCC8 p.Asp1408fs (c.4220_4221insACAGG) is absent from gnomAD (gnomAD).

ABCC8 p.Asp1408fs

c.4220_4221insACAGG · rs2496450975 · VCV1726804

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 35 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.3	GERP -5.1

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.Asp1408fs
Coding: c.4220_4221insACAGG
MANE Select: NM_000352
dbSNP: rs2496450975
Type: Insertion
Location: chr11:17395696 (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 1408: a β-strand; the abc transporter 2 domain

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.Ala161delinsArgCysValTer Likely pathogenic ★ same condition
ABCC8 p.Arg258fs Likely pathogenic ★ same condition
ABCC8 p.Gly1089fs Likely pathogenic ★ same condition
ABCC8 p.Ala535fs Uncertain significance ★ same condition
ABCC8 p.Lys1343fs Uncertain significance ★ same condition
ABCC8 p.Asp1408= Likely benign ★ same residue
ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1333-1013A>G 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-asp1408fs (accessed [today's date]).

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