Is ABCC8 p.Ala870= (c.2610C>T) pathogenic?

ABCC8 p.Ala870= (c.2610C>T) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-28). Rare (popmax 0.336%, afr); Associated with transient neonatal diabetes mellitus.

What condition is associated with ABCC8 p.Ala870= (c.2610C>T)?

ABCC8 p.Ala870= (c.2610C>T) is associated with transient neonatal diabetes mellitus, hyperinsulinemic hypoglycemia, familial, 1, diabetes mellitus, transient neonatal, 2 (ClinVar).

How common is ABCC8 p.Ala870= (c.2610C>T) in the general population?

ABCC8 p.Ala870= (c.2610C>T) is rare (popmax 0.336%, afr) (gnomAD).

ABCC8 p.Ala870=

c.2610C>T · rs111967655 · VCV195647

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.336%, afr)

Conditions

transient neonatal diabetes mellitus

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 -8.3	GERP -5.6
Overall
CADD	1.586	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.336% African / African-American · 252/75,014 alleles

Filtering AF 0.302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.289%

Overall 0.0347% 560/1,614,122 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.336%	298
Ashkenazi Jewishnot grpmax-eligible	0.26%	385
Admixed American	0.147%	682
Middle Eastern	0.115%	866
Remaining individualsnot grpmax-eligible	0.088%	1,137
European (non-Finnish)	0.00661%	15,128
South Asian	0.00329%	30,362

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.Ala870=
Coding: c.2610C>T
MANE Select: NM_000352
dbSNP: rs111967655
Type: single nucleotide variant
Location: chr11:17410600 (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 870: an α-helix; the abc transporter 1 domain

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

Disease context

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

Also linked: hyperinsulinemic hypoglycemia, familial, 1 diabetes mellitus, transient neonatal, 2 maturity-onset diabetes of the young permanent neonatal diabetes mellitus

Similar variants

ABCC8 p.Ala870Val Pathogenic ★ ⚠ 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
ABCC8 c.1630+1G>T Pathogenic ★★ same condition
ABCC8 c.1817+2T>C 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-ala870 (accessed [today's date]).

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