Is ABCC8 p.Glu100Ter (c.298G>T) pathogenic?

ABCC8 p.Glu100Ter (c.298G>T) is classified Pathogenic in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-22). Very rare (popmax 0.00223%, eas); Associated with type 2 diabetes mellitus.

What condition is associated with ABCC8 p.Glu100Ter (c.298G>T)?

ABCC8 p.Glu100Ter (c.298G>T) is associated with type 2 diabetes mellitus (ClinVar).

How common is ABCC8 p.Glu100Ter (c.298G>T) in the general population?

ABCC8 p.Glu100Ter (c.298G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

ABCC8 p.Glu100Ter

c.298G>T · rs200687571 · VCV2735554

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

type 2 diabetes mellitus

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 39
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.4, phastCons 1
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 0.00223% East Asian · 1/44,876 alleles

Overall 6.84e-05% 1/1,461,816 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
Protein: p.Glu100Ter
Coding: c.298G>T
MANE Select: NM_000352
dbSNP: rs200687571
Type: single nucleotide variant
Location: chr11:17470215 (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 100: a β-strand; a UniProt-annotated variant site (found in a patient with clinical features of diabetes; uncertain significance)

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

Disease context

type 2 diabetes mellitus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCC8 p.Glu100Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCC8 p.Glu100= Likely benign ★ same residue
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.1630+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1630+1G>T Pathogenic ★★ same condition
ABCC8 c.1817+1G>C 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-glu100ter (accessed [today's date]).

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