Is ABCC8 p.Ala1152Val (c.3455C>T) pathogenic?

ABCC8 p.Ala1152Val (c.3455C>T) is classified Uncertain significance in ABCC8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-03). AlphaMissense: likely pathogenic (0.8782); Very rare (popmax 8.47e-05%, nfe); Associated with transient neonatal diabetes mellitus.

What condition is associated with ABCC8 p.Ala1152Val (c.3455C>T)?

ABCC8 p.Ala1152Val (c.3455C>T) is associated with transient neonatal diabetes mellitus, maturity-onset diabetes of the young (ClinVar).

How common is ABCC8 p.Ala1152Val (c.3455C>T) in the general population?

ABCC8 p.Ala1152Val (c.3455C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABCC8 p.Ala1152Val (c.3455C>T)?

AlphaMissense predicts likely pathogenic (score 0.8782) — an in-silico prediction, not a clinical call.

ABCC8 p.Ala1152Val

c.3455C>T · rs1354859002 · VCV446769

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8782 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

transient neonatal diabetes mellitus

Computational evidence

Protein change
AlphaMissense	0.8782	likely pathogenic
REVEL	0.704	pathogenic-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,992 alleles

Overall 0.000657% 1/152,180 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.Ala1152Val
Coding: c.3455C>T
MANE Select: NM_000352
dbSNP: rs1354859002
Type: single nucleotide variant
Location: chr11:17404614 (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 1152: an α-helix; the abc transmembrane type-1 2 domain

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.Ala1152Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCC8 p.Ala1152Asp Uncertain significance ★★ ⚠ same residue
ABCC8 p.Ala1152= Likely benign ★★ 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

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-ala1152val (accessed [today's date]).

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