Is ABCC8 p.Arg1273= (c.3819G>A) pathogenic?

ABCC8 p.Arg1273= (c.3819G>A) is classified Benign in ABCC8 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 71.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with diabetes mellitus, permanent neonatal 3.

What condition is associated with ABCC8 p.Arg1273= (c.3819G>A)?

ABCC8 p.Arg1273= (c.3819G>A) is associated with diabetes mellitus, permanent neonatal 3, type 2 diabetes mellitus, hypoglycemia, leucine-induced (ClinVar).

How is Isolated permanent neonatal diabetes mellitus inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCC8 p.Arg1273=

Q: How common is ABCC8 p.Arg1273= (c.3819G>A) in the general population?

ABCC8 p.Arg1273= (c.3819G>A) is common (popmax 71.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3819G>A · rs1799859 · VCV157698

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 71.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

diabetes mellitus, permanent neonatal 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.086	GERP -3, phastCons 0.005
Overall
CADD	9.866	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 71.4% African / African-American · 53,545/74,992 alleles

Filtering AF 70.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 70.7%

Overall 28.9% 465,794/1,613,552 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	71.4%	1
Middle Eastern	39.8%	3
Admixed American	39.3%	3
South Asian	29.8%	3
Remaining individualsnot grpmax-eligible	29.3%	3
European (non-Finnish)	27%	4
Ashkenazi Jewishnot grpmax-eligible	25.4%	4
Amishnot grpmax-eligible	18.6%	5
Finnishnot grpmax-eligible	15.9%	6
East Asian	9.97%	10

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.Arg1273=
Coding: c.3819G>A
MANE Select: NM_000352
dbSNP: rs1799859
Type: single nucleotide variant
Location: chr11:17397732 (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 1273: the abc transmembrane type-1 2 domain

Full ABCC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

diabetes mellitus, permanent neonatal 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: type 2 diabetes mellitus hypoglycemia, leucine-induced hyperinsulinemic hypoglycemia, familial, 1 diabetes mellitus, transient neonatal, 2

For Isolated permanent neonatal diabetes mellitus (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ABCC8 p.Arg1273Trp Uncertain significance ★★ ⚠ same residue
ABCC8 p.Arg1273Gly Uncertain significance ★ ⚠ same residue
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

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-arg1273 (accessed [today's date]).

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