Is ABCC8 p.Ile1549= (c.4647C>T) pathogenic?

ABCC8 p.Ile1549= (c.4647C>T) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-29). Ultra-rare (popmax 0.0535%, eas); Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Ile1549= (c.4647C>T)?

ABCC8 p.Ile1549= (c.4647C>T) is associated with Inborn genetic diseases, hyperinsulinemic hypoglycemia, familial, 1, diabetes mellitus, transient neonatal, 2 (ClinVar).

How common is ABCC8 p.Ile1549= (c.4647C>T) in the general population?

ABCC8 p.Ile1549= (c.4647C>T) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

ABCC8 p.Ile1549=

c.4647C>T · rs367862706 · VCV303748

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9
Overall
CADD	2.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0535% East Asian · 24/44,836 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00304% 49/1,612,802 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0535%	1,868
Finnishnot grpmax-eligible	0.0141%	7,077
Remaining individualsnot grpmax-eligible	0.00961%	10,406
South Asian	0.00549%	18,212
European (non-Finnish)	0.000424%	235,858

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.Ile1549=
Coding: c.4647C>T
MANE Select: NM_000352
dbSNP: rs367862706
Type: single nucleotide variant
Location: chr11:17393090 (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 1549: a β-strand; the abc transporter 2 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: hyperinsulinemic hypoglycemia, familial, 1 diabetes mellitus, transient neonatal, 2 maturity-onset diabetes of the young transient neonatal diabetes mellitus permanent neonatal diabetes mellitus

Similar variants

ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.148+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.148+2T>G Likely pathogenic ★★ same condition
ABCC8 c.1630+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1630+1G>T Pathogenic ★★ same condition
ABCC8 c.1817+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.2041-21G>A 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-ile1549 (accessed [today's date]).

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