Is ABCC8 p.Arg825Gln (c.2474G>A) pathogenic?

ABCC8 p.Arg825Gln (c.2474G>A) is classified Uncertain significance in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: ambiguous (0.4608); Very rare (popmax 0.0011%, nfe).

How common is ABCC8 p.Arg825Gln (c.2474G>A) in the general population?

ABCC8 p.Arg825Gln (c.2474G>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about ABCC8 p.Arg825Gln (c.2474G>A)?

AlphaMissense predicts ambiguous (score 0.4608) — an in-silico prediction, not a clinical call.

ABCC8 p.Arg825Gln

c.2474G>A · rs375172221 · VCV3253423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4608 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4608	ambiguous
REVEL	0.61	indeterminate
SaProt	LLR -9.22	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,180,044 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000867% 14/1,614,100 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0011%	90,773
South Asian	0.0011%	91,084

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.Arg825Gln
Coding: c.2474G>A
MANE Select: NM_000352
dbSNP: rs375172221
Type: single nucleotide variant
Location: chr11:17413395 (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

Similar variants

ABCC8 p.Arg825Trp Pathogenic ★★ same residue
ABCC8 p.Arg825Leu Uncertain significance ★★ same residue
ABCC8 p.Arg825= Likely benign ★★ same residue
ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.148+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.148+2T>G Likely pathogenic ★★ same type
ABCC8 c.1630+1G>A Pathogenic/Likely pathogenic ★★ same type

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-arg825gln (accessed [today's date]).

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