Is ABCC8 p.Ala554= (c.1662T>G) pathogenic?

ABCC8 p.Ala554= (c.1662T>G) is classified Likely benign in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-24). Ultra-rare (popmax 0.0191%, afr); Associated with hypoglycemia, leucine-induced.

What condition is associated with ABCC8 p.Ala554= (c.1662T>G)?

ABCC8 p.Ala554= (c.1662T>G) is associated with hypoglycemia, leucine-induced, type 2 diabetes mellitus, hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 p.Ala554= (c.1662T>G) in the general population?

ABCC8 p.Ala554= (c.1662T>G) is ultra-rare (popmax 0.0191%, afr) (gnomAD).

ABCC8 p.Ala554=

c.1662T>G · rs368782953 · VCV1132494

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0191%, afr)

Conditions

hypoglycemia, leucine-induced

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 -5.7	GERP -4.8
Overall
CADD	0.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0191% African / African-American · 14/73,152 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00925%

Overall 0.00103% 16/1,552,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0191%	5,225
Admixed American	0.00195%	51,166
Remaining individualsnot grpmax-eligible	0.00166%	60,198

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.Ala554=
Coding: c.1662T>G
MANE Select: NM_000352
dbSNP: rs368782953
Type: single nucleotide variant
Location: chr11:17432213 (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 554: 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

hypoglycemia, leucine-induced — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: type 2 diabetes mellitus hyperinsulinemic hypoglycemia, familial, 1 diabetes mellitus, transient neonatal, 2 diabetes mellitus, permanent neonatal 3

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+1G>C Pathogenic ★★ same condition
ABCC8 c.1817+2T>C 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-ala554 (accessed [today's date]).

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