Is ABCC8 p.Phe198del (c.589TTC[1]) pathogenic?

ABCC8 p.Phe198del (c.589TTC[1]) is classified Uncertain significance in ABCC8 (ClinVar, Single submitter, 2 submitters). Very rare (popmax 0.00167%, amr); Associated with transient neonatal diabetes mellitus.

What condition is associated with ABCC8 p.Phe198del (c.589TTC[1])?

ABCC8 p.Phe198del (c.589TTC[1]) is associated with transient neonatal diabetes mellitus, hyperinsulinemic hypoglycemia, familial, 1, maturity-onset diabetes of the young (ClinVar).

How common is ABCC8 p.Phe198del (c.589TTC[1]) in the general population?

ABCC8 p.Phe198del (c.589TTC[1]) is very rare (popmax 0.00167%, amr) (gnomAD).

ABCC8 p.Phe198del

c.589TTC[1] · rs772409200 · VCV550521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

transient neonatal diabetes mellitus

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,024 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000958% 14/1,461,854 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,024
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.00102%	98,334

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.Phe198del
Coding: c.589TTC[1]
MANE Select: NM_000352
dbSNP: rs772409200
Type: Microsatellite
Location: chr11:17461811 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 8 PDB

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: hyperinsulinemic hypoglycemia, familial, 1 maturity-onset diabetes of the young

Similar variants

ABCC8 p.Ser1276fs Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1817+2_1817+6del Uncertain significance ★ same condition
ABCC8 p.Arg1486fs Uncertain significance ★ same condition
ABCC8 p.Asp760fs Conflicting classifications of pathogenicity ★ same condition
ABCC8 p.Cys87fs Uncertain significance ★ same condition
ABCC8 p.Leu225del Uncertain significance ★ same condition
ABCC8 p.Phe198Leu Uncertain significance ★ ⚠ same residue
ABCC8 p.Ser1386del Conflicting classifications of pathogenicity ★ 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-phe198del (accessed [today's date]).

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