Is ABCC8 p.Arg16= (c.48G>A) pathogenic?

ABCC8 p.Arg16= (c.48G>A) is classified Likely benign in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-08). Very rare (popmax 0.00145%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Arg16= (c.48G>A)?

ABCC8 p.Arg16= (c.48G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC8 p.Arg16= (c.48G>A) in the general population?

ABCC8 p.Arg16= (c.48G>A) is very rare (popmax 0.00145%, nfe) (gnomAD).

ABCC8 p.Arg16=

c.48G>A · rs750383415 · VCV1625490

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00145%, nfe)

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 0.72	GERP -1.8, phastCons 1
Overall
CADD	15.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00145% European (non-Finnish) · 17/1,176,450 alleles

Filtering AF 0.00088% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00072%

Overall 0.00137% 22/1,605,676 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00644%	15,531
European (non-Finnish)grpmax	0.00145%	69,203
African / African-American	0.00134%	74,520

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg16=
Coding: c.48G>A
MANE Select: NM_000352
dbSNP: rs750383415
Type: single nucleotide variant
Location: chr11:17476729 (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 16: a disulfide bond

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

Similar variants

ABCC8 p.Arg16Trp Uncertain significance ★★ ⚠ same residue
ABCC8 p.Arg16Pro Uncertain significance ★ ⚠ same residue
ABCC8 p.Arg1250Ter Pathogenic ★★ same condition
ABCC8 c.1923+3G>A Uncertain significance ★★ same condition
ABCC8 p.Ala365Val Uncertain significance ★★ ⚠ same condition
ABCC8 p.Ala478Ser Uncertain significance ★★ ⚠ same condition
ABCC8 p.Arg657Gln Uncertain significance ★★ ⚠ same condition
ABCC8 p.Arg992Pro Uncertain significance ★★ ⚠ 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-arg16 (accessed [today's date]).

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