Is ABCC8 p.Asp1447fs (c.4340_4362del) pathogenic?

ABCC8 p.Asp1447fs (c.43404362del) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-05-13). Absent from gnomAD; Associated with maturity-onset diabetes of the young.

What condition is associated with ABCC8 p.Asp1447fs (c.4340_4362del)?

ABCC8 p.Asp1447fs (c.4340_4362del) is associated with maturity-onset diabetes of the young, hyperinsulinemic hypoglycemia, familial, 1, transient neonatal diabetes mellitus (ClinVar).

How common is ABCC8 p.Asp1447fs (c.4340_4362del) in the general population?

ABCC8 p.Asp1447fs (c.4340_4362del) is absent from gnomAD (gnomAD).

How is MODY inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

ABCC8 p.Asp1447fs

c.4340_4362del · rs1554904554 · VCV557349

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

maturity-onset diabetes of the young

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 36 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, 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.Asp1447fs
Coding: c.4340_4362del
MANE Select: NM_000352
dbSNP: rs1554904554
Type: Deletion
Location: chr11:17395221 (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 1447: the abc transporter 2 domain

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

Disease context

maturity-onset diabetes of the young — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hyperinsulinemic hypoglycemia, familial, 1 transient neonatal diabetes mellitus

For MODY (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

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-asp1447fs (accessed [today's date]).

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