Is ABCC8 p.Phe545fs (c.1634del) pathogenic?

ABCC8 p.Phe545fs (c.1634del) is classified Pathogenic in ABCC8 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2024-05-07). Very rare (popmax 0.00196%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Phe545fs (c.1634del)?

ABCC8 p.Phe545fs (c.1634del) is associated with Inborn genetic diseases, type 2 diabetes mellitus, hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 p.Phe545fs (c.1634del) in the general population?

ABCC8 p.Phe545fs (c.1634del) is very rare (popmax 0.00196%, amr) (gnomAD).

ABCC8 p.Phe545fs

c.1634del · rs1260178539 · VCV446765

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Conditions

Inborn genetic diseases

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 11 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00196% Admixed American · 1/51,052 alleles

Overall 7.14e-05% 1/1,400,002 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.Phe545fs
Coding: c.1634del
MANE Select: NM_000352
dbSNP: rs1260178539
Type: Deletion
Location: chr11:17432241 (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 545: an α-helix; the abc transmembrane type-1 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: type 2 diabetes mellitus hyperinsulinemic hypoglycemia, familial, 1 neonatal diabetes mellitus familial hyperinsulinism maturity-onset diabetes of the young

Similar variants

ABCC8 p.Ala269fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Gln19fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Gln273fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Gln632fs Pathogenic ★★ same condition
ABCC8 p.His627fs Pathogenic ★★ same condition
ABCC8 p.Ile450fs Pathogenic ★★ same condition
ABCC8 p.Ile550fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Leu1170fs 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-phe545fs (accessed [today's date]).

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