Is ABCC8 p.Ala294= (c.882C>G) pathogenic?

ABCC8 p.Ala294= (c.882C>G) is classified Uncertain significance in ABCC8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-01). Absent from gnomAD v4.1; Associated with Hereditary hyperinsulinism.

What condition is associated with ABCC8 p.Ala294= (c.882C>G)?

ABCC8 p.Ala294= (c.882C>G) is associated with Hereditary hyperinsulinism (ClinVar).

How common is ABCC8 p.Ala294= (c.882C>G) in the general population?

ABCC8 p.Ala294= (c.882C>G) is absent from gnomAD v4.1 (gnomAD).

ABCC8 p.Ala294=

c.882C>G · VCV4063617

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Hereditary hyperinsulinism

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.3, phastCons 1
Overall
CADD	13.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC8
Protein: p.Ala294=
Coding: c.882C>G
MANE Select: NM_000352
Type: single nucleotide variant
Location: chr11:17460617 (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 294: an α-helix

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

Disease context

Hereditary hyperinsulinism

Similar variants

ABCC8 p.Ala294Asp Uncertain significance ★ ⚠ same residue
ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.2116+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.2117-1G>A Pathogenic ★★ same condition
ABCC8 c.2475+2T>A Likely pathogenic ★★ same condition
ABCC8 c.3988+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.3989-9G>A 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-ala294 (accessed [today's date]).

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