Is ABCC8 p.Phe432= (c.1296C>T) pathogenic?

ABCC8 p.Phe432= (c.1296C>T) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-08-22). Absent from gnomAD v4.1; Associated with transient neonatal diabetes mellitus.

What condition is associated with ABCC8 p.Phe432= (c.1296C>T)?

ABCC8 p.Phe432= (c.1296C>T) is associated with transient neonatal diabetes mellitus, maturity-onset diabetes of the young (ClinVar).

How common is ABCC8 p.Phe432= (c.1296C>T) in the general population?

ABCC8 p.Phe432= (c.1296C>T) is absent from gnomAD v4.1 (gnomAD).

ABCC8 p.Phe432=

c.1296C>T · rs1591845922 · VCV799568

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

transient neonatal diabetes mellitus

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.41	donor loss, 36 bp away · masked 0 · deltas
Pangolin	Δ0.22	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.5	GERP -1.1, phastCons 1
Overall
CADD	10.59	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.Phe432=
Coding: c.1296C>T
MANE Select: NM_000352
dbSNP: rs1591845922
Type: single nucleotide variant
Location: chr11:17448552 (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 432: a turn; the abc transmembrane type-1 1 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 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
ABCC8 p.Gly716Ser 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-phe432 (accessed [today's date]).

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