Is ABCC8 p.Asp760fs (c.2277_2280del) pathogenic?

ABCC8 p.Asp760fs (c.22772280del) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-03-15). Absent from gnomAD; Associated with transient neonatal diabetes mellitus.

What condition is associated with ABCC8 p.Asp760fs (c.2277_2280del)?

ABCC8 p.Asp760fs (c.2277_2280del) is associated with transient neonatal diabetes mellitus, maturity-onset diabetes of the young (ClinVar).

How common is ABCC8 p.Asp760fs (c.2277_2280del) in the general population?

ABCC8 p.Asp760fs (c.2277_2280del) is absent from gnomAD (gnomAD).

ABCC8 p.Asp760fs

c.2277_2280del · rs1955018104 · VCV836622

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

transient neonatal diabetes mellitus

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 18 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.6	GERP -3.6

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.Asp760fs
Coding: c.2277_2280del
MANE Select: NM_000352
dbSNP: rs1955018104
Type: Microsatellite
Location: chr11:17415315 (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 760: the abc transporter 1 domain

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

Disease context

transient neonatal diabetes mellitus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: maturity-onset diabetes of the young

Similar variants

ABCC8 p.Asp760Asn Uncertain significance ★★ ⚠ same residue
ABCC8 p.Asp760Glu Uncertain significance ★★ ⚠ same residue
ABCC8 c.1817+2_1817+6del Uncertain significance ★ same condition
ABCC8 p.Arg1486fs Uncertain significance ★ same condition
ABCC8 p.Asp760Val Uncertain significance ★ ⚠ same residue
ABCC8 p.Phe198del Uncertain significance ★ same condition
ABCC8 p.Ser1386del Conflicting classifications of pathogenicity ★ same condition
ABCC8 p.Thr1044_Pro1045insLeuThr Uncertain significance ★ 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-asp760fs (accessed [today's date]).

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