Is ABCC8 p.Ala110= (c.330C>T) pathogenic?

ABCC8 p.Ala110= (c.330C>T) is classified Benign/Likely benign in ABCC8 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 13.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with diabetes mellitus, permanent neonatal 3.

What condition is associated with ABCC8 p.Ala110= (c.330C>T)?

ABCC8 p.Ala110= (c.330C>T) is associated with diabetes mellitus, permanent neonatal 3, type 2 diabetes mellitus, hypoglycemia, leucine-induced (ClinVar).

How is Isolated permanent neonatal diabetes mellitus inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCC8 p.Ala110=

Q: How common is ABCC8 p.Ala110= (c.330C>T) in the general population?

ABCC8 p.Ala110= (c.330C>T) is common (popmax 13.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.330C>T · rs8192695 · VCV157695

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 13.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

diabetes mellitus, permanent neonatal 3

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 -11	GERP -4.9
Overall
CADD	1.703	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.4% African / African-American · 10,082/75,004 alleles

Filtering AF 13.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.1%

Overall 4.53% 73,054/1,614,062 alleles · common exomes 63,094/1,461,852 · genomes 9,960/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.4%	7
South Asian	7.02%	14
Finnishnot grpmax-eligible	4.9%	20
Ashkenazi Jewishnot grpmax-eligible	4.67%	21
Remaining individualsnot grpmax-eligible	4.56%	22
European (non-Finnish)	4%	25
Amishnot grpmax-eligible	3.74%	27
Admixed American	2.16%	46
Middle Eastern	1.98%	51
East Asian	1.13%	89

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.Ala110=
Coding: c.330C>T
MANE Select: NM_000352
dbSNP: rs8192695
Type: single nucleotide variant
Location: chr11:17470183 (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 110: an α-helix

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

Disease context

diabetes mellitus, permanent neonatal 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: type 2 diabetes mellitus hypoglycemia, leucine-induced hyperinsulinemic hypoglycemia, familial, 1 diabetes mellitus, transient neonatal, 2 permanent neonatal diabetes mellitus

For Isolated permanent neonatal diabetes mellitus (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ABCC8 p.Ala110Thr Uncertain significance ★ same residue
ABCC8 p.Ala110Val Uncertain significance ★ ⚠ 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

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-ala110 (accessed [today's date]).

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