Is ABCC8 p.Ala625Val (c.1874C>T) pathogenic?

ABCC8 p.Ala625Val (c.1874C>T) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.07); Rare (popmax 0.288%, afr); Associated with monogenic diabetes.

What condition is associated with ABCC8 p.Ala625Val (c.1874C>T)?

ABCC8 p.Ala625Val (c.1874C>T) is associated with monogenic diabetes (ClinVar).

How common is ABCC8 p.Ala625Val (c.1874C>T) in the general population?

ABCC8 p.Ala625Val (c.1874C>T) is rare (popmax 0.288%, afr) (gnomAD).

What do computational predictors say about ABCC8 p.Ala625Val (c.1874C>T)?

AlphaMissense predicts likely benign (score 0.07) — an in-silico prediction, not a clinical call.

ABCC8 p.Ala625Val

c.1874C>T · rs148709148 · VCV596784

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.07 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.288%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

monogenic diabetes

Computational evidence

Protein change
AlphaMissense	0.07	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -0.026, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	18.03	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 0.288% African / African-American · 216/75,060 alleles

Filtering AF 0.256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.244%

Overall 0.015% 242/1,614,010 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.288%	347
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.0183%	5,457
European (non-Finnish)	8.47e-05%	1,180,022

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.Ala625Val
Coding: c.1874C>T
MANE Select: NM_000352
dbSNP: rs148709148
Type: single nucleotide variant
Location: chr11:17428614 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 8 PDB

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

Disease context

monogenic diabetes — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCC8 p.Arg1379Cys Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Arg1379His Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Arg998Ter Pathogenic ★★ same condition
ABCC8 p.Arg1273Trp Uncertain significance ★★ ⚠ same condition
ABCC8 p.Arg1379Ser Uncertain significance ★★ ⚠ same condition
ABCC8 p.Asn1292Ser Uncertain significance ★★ ⚠ same condition
ABCC8 p.Asn1348Ser Uncertain significance ★★ ⚠ same condition
ABCC8 p.Gly296Arg 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-ala625val (accessed [today's date]).

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