Is ABCC8 p.Ala294Asp (c.881C>A) pathogenic?

ABCC8 p.Ala294Asp (c.881C>A) is classified Uncertain significance in ABCC8 (ClinVar, Single submitter, 2 submitters). AlphaMissense: likely pathogenic (0.9176); Absent from gnomAD v4.1; Associated with transient neonatal diabetes mellitus.

What condition is associated with ABCC8 p.Ala294Asp (c.881C>A)?

ABCC8 p.Ala294Asp (c.881C>A) is associated with transient neonatal diabetes mellitus, maturity-onset diabetes of the young (ClinVar).

How common is ABCC8 p.Ala294Asp (c.881C>A) in the general population?

ABCC8 p.Ala294Asp (c.881C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC8 p.Ala294Asp (c.881C>A)?

AlphaMissense predicts likely pathogenic (score 0.9176) — an in-silico prediction, not a clinical call.

ABCC8 p.Ala294Asp

c.881C>A · rs1957153674 · VCV991060

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9176 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

transient neonatal diabetes mellitus

Computational evidence

Protein change
AlphaMissense	0.9176	likely pathogenic
REVEL	0.831	moderately pathogenic-leaning
SaProt	LLR -16.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ala294Asp
Coding: c.881C>A
MANE Select: NM_000352
dbSNP: rs1957153674
Type: single nucleotide variant
Location: chr11:17460618 (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

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.Ala294= Uncertain significance same residue
ABCC8 c.2116+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.3868-1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.3989-9G>A Pathogenic ★★ same condition
ABCC8 c.4308-2A>G Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Arg1379His Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Arg1538Gln Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Gly228Asp 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-ala294asp (accessed [today's date]).

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