Is ABCC8 p.Arg825= (c.2473C>A) pathogenic?

ABCC8 p.Arg825= (c.2473C>A) is classified Likely benign in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-24). Very rare (popmax 0.00445%, eas); Associated with hypoglycemia, leucine-induced.

What condition is associated with ABCC8 p.Arg825= (c.2473C>A)?

ABCC8 p.Arg825= (c.2473C>A) is associated with hypoglycemia, leucine-induced, type 2 diabetes mellitus, hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 p.Arg825= (c.2473C>A) in the general population?

ABCC8 p.Arg825= (c.2473C>A) is very rare (popmax 0.00445%, eas) (gnomAD).

ABCC8 p.Arg825=

c.2473C>A · rs779736828 · VCV1626109

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Conditions

hypoglycemia, leucine-induced

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.8	GERP 0.068, phastCons 1
Overall
CADD	18.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,894 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00229% 37/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,447
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.00263%	38,066
Admixed American	0.00167%	59,998
African / African-American	0.00133%	74,922

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.Arg825=
Coding: c.2473C>A
MANE Select: NM_000352
dbSNP: rs779736828
Type: single nucleotide variant
Location: chr11:17413396 (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 825: a β-strand; the abc transporter 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 p.Arg825Trp Pathogenic ★★ same residue
ABCC8 p.Arg825Leu Uncertain significance ★★ ⚠ same residue
ABCC8 p.Arg825Gln 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

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-arg825 (accessed [today's date]).

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