Is ABCC8 p.Ile76fs (c.227del) pathogenic?

ABCC8 p.Ile76fs (c.227del) is classified Pathogenic in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-06). Absent from gnomAD.

How common is ABCC8 p.Ile76fs (c.227del) in the general population?

ABCC8 p.Ile76fs (c.227del) is absent from gnomAD (gnomAD).

ABCC8 p.Ile76fs

c.227del · rs2496918974 · VCV2701295

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP -3.2, 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.Ile76fs
Coding: c.227del
MANE Select: NM_000352
dbSNP: rs2496918974
Type: Deletion
Location: chr11:17474949 (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 76: an α-helix

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

Similar variants

ABCC8 p.Ile76Val Uncertain significance ★ same residue
ABCC8 p.Ile76= Likely benign ★ same residue
ABCC8 p.Ala269fs Pathogenic/Likely pathogenic ★★ same type
ABCC8 p.Gln19fs Pathogenic/Likely pathogenic ★★ same type
ABCC8 p.Gln273fs Pathogenic/Likely pathogenic ★★ same type
ABCC8 p.Gln632fs Pathogenic ★★ same type
ABCC8 p.His627fs Pathogenic ★★ same type
ABCC8 p.Ile450fs Pathogenic ★★ same type

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-ile76fs (accessed [today's date]).

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