Is ABCC8 p.Phe1576= (c.4728C>T) pathogenic?

ABCC8 p.Phe1576= (c.4728C>T) is classified Benign/Likely benign in ABCC8 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.84%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Phe1576= (c.4728C>T)?

ABCC8 p.Phe1576= (c.4728C>T) is associated with Inborn genetic diseases, hyperinsulinemic hypoglycemia, familial, 1, diabetes mellitus, transient neonatal, 2 (ClinVar).

How common is ABCC8 p.Phe1576= (c.4728C>T) in the general population?

ABCC8 p.Phe1576= (c.4728C>T) is low-frequency (popmax 3.84%, afr) (gnomAD).

ABCC8 p.Phe1576=

c.4728C>T · rs73419228 · VCV157706

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.84%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.5
Overall
CADD	5.531	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.84% African / African-American · 2,884/75,062 alleles

Filtering AF 3.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.68%

Overall 0.222% 3,585/1,614,152 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.84%	26
Middle Eastern	0.627%	160
Admixed American	0.297%	337
Remaining individualsnot grpmax-eligible	0.285%	351
South Asian	0.0242%	4,140
European (non-Finnish)	0.0242%	4,141

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.Phe1576=
Coding: c.4728C>T
MANE Select: NM_000525 · reported on NM_000352
dbSNP: rs73419228
Type: single nucleotide variant
Location: chr11:17393009 (GRCh38)

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

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-phe1576 (accessed [today's date]).

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