Is ABCC8 p.Gln273fs (c.817del) pathogenic?

ABCC8 p.Gln273fs (c.817del) is classified Pathogenic/Likely pathogenic in ABCC8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-27). Absent from gnomAD; Associated with Hereditary hyperinsulinism.

What condition is associated with ABCC8 p.Gln273fs (c.817del)?

ABCC8 p.Gln273fs (c.817del) is associated with Hereditary hyperinsulinism, type 2 diabetes mellitus (ClinVar).

How common is ABCC8 p.Gln273fs (c.817del) in the general population?

ABCC8 p.Gln273fs (c.817del) is absent from gnomAD (gnomAD).

ABCC8 p.Gln273fs

c.817del · rs2133678848 · VCV1453604

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Hereditary hyperinsulinism

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 5 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 2.3, 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.Gln273fs
Coding: c.817del
MANE Select: NM_000352
dbSNP: rs2133678848
Type: Deletion
Location: chr11:17461588 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 8 PDB

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

Disease context

Hereditary hyperinsulinism

Also linked: type 2 diabetes mellitus

Similar variants

ABCC8 p.Ala269fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Gln19fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Gln273Ter Pathogenic/Likely pathogenic ★★ same residue
ABCC8 p.Gln632fs Pathogenic ★★ same condition
ABCC8 p.His627fs Pathogenic ★★ same condition
ABCC8 p.Ile550fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Leu1170fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Leu1430fs 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-gln273fs (accessed [today's date]).

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