Is ABCC8 p.Ser541fs (c.1620dup) pathogenic?

ABCC8 p.Ser541fs (c.1620dup) is classified Likely pathogenic in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-26). Associated with Hereditary hyperinsulinism.

What condition is associated with ABCC8 p.Ser541fs (c.1620dup)?

ABCC8 p.Ser541fs (c.1620dup) is associated with Hereditary hyperinsulinism (ClinVar).

ABCC8 p.Ser541fs

c.1620dup · VCV4818235

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Hereditary hyperinsulinism

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 10 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1

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

Variant & gene context

Gene: ABCC8
Protein: p.Ser541fs
Coding: c.1620dup
MANE Select: NM_000352
Type: Duplication
Location: chr11:17442729 (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 541: 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

Hereditary hyperinsulinism

Similar variants

ABCC8 p.Ser752fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Val28fs Pathogenic ★★ same condition
ABCC8 p.Leu1282fs Likely pathogenic ★ same condition
ABCC8 p.Lys528fs Likely pathogenic ★ same condition
ABCC8 p.Phe1216fs Likely pathogenic ★ same condition
ABCC8 c.4307+9dup Uncertain significance same condition
ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1333-1013A>G 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-ser541fs (accessed [today's date]).

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