Is ABCC8 p.Val560Met (c.1678G>A) pathogenic?

ABCC8 p.Val560Met (c.1678G>A) is classified Benign/Likely benign in ABCC8 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.113); Low-frequency (popmax 1.16%, eas); Associated with diabetes mellitus, transient neonatal, 2.

What condition is associated with ABCC8 p.Val560Met (c.1678G>A)?

ABCC8 p.Val560Met (c.1678G>A) is associated with diabetes mellitus, transient neonatal, 2, hyperinsulinemic hypoglycemia, familial, 1, permanent neonatal diabetes mellitus (ClinVar).

How common is ABCC8 p.Val560Met (c.1678G>A) in the general population?

ABCC8 p.Val560Met (c.1678G>A) is low-frequency (popmax 1.16%, eas) (gnomAD).

What do computational predictors say about ABCC8 p.Val560Met (c.1678G>A)?

AlphaMissense predicts likely benign (score 0.113) — an in-silico prediction, not a clinical call.

ABCC8 p.Val560Met

c.1678G>A · rs4148619 · VCV188919

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.113 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.16%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

diabetes mellitus, transient neonatal, 2

Computational evidence

Protein change
AlphaMissense	0.113	likely benign
REVEL	0.505	indeterminate
SaProt	LLR -8.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.001, phastCons 0.81
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	21.3	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 1.16% East Asian · 522/44,880 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.0347% 560/1,614,080 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.16%	86
Remaining individualsnot grpmax-eligible	0.0256%	3,906
South Asian	0.00549%	18,216
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Finnishnot grpmax-eligible	0.00156%	63,990
African / African-American	0.00133%	75,066
European (non-Finnish)	0.00119%	84,283

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.Val560Met
Coding: c.1678G>A
MANE Select: NM_000352
dbSNP: rs4148619
Type: single nucleotide variant
Location: chr11:17430953 (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 560: a UniProt-annotated variant site (in); an α-helix; the abc transmembrane type-1 1 domain

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

Disease context

diabetes mellitus, transient neonatal, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hyperinsulinemic hypoglycemia, familial, 1 permanent neonatal diabetes mellitus

Similar variants

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
ABCC8 c.1817+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.2041-21G>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-val560met (accessed [today's date]).

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