Is ABCC8 p.Ala315= (c.945C>T) pathogenic?

ABCC8 p.Ala315= (c.945C>T) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-04). Rare (popmax 0.528%, afr); Associated with transient neonatal diabetes mellitus.

What condition is associated with ABCC8 p.Ala315= (c.945C>T)?

ABCC8 p.Ala315= (c.945C>T) is associated with transient neonatal diabetes mellitus, maturity-onset diabetes of the young (ClinVar).

How common is ABCC8 p.Ala315= (c.945C>T) in the general population?

ABCC8 p.Ala315= (c.945C>T) is rare (popmax 0.528%, afr) (gnomAD).

ABCC8 p.Ala315=

c.945C>T · rs138521721 · VCV730708

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.528%, 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 -15	GERP -4.9
Overall
CADD	0.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.528% African / African-American · 396/75,046 alleles

Filtering AF 0.485% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.468%

Overall 0.0263% 424/1,614,018 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.528%	190
Remaining individualsnot grpmax-eligible	0.0192%	5,209
Admixed American	0.00999%	10,006
South Asian	0.00439%	22,772
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
East Asian	0.00223%	44,882
European (non-Finnish)	0.000339%	295,011

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.Ala315=
Coding: c.945C>T
MANE Select: NM_000352
dbSNP: rs138521721
Type: single nucleotide variant
Location: chr11:17460554 (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 315: the abc transmembrane type-1 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: maturity-onset diabetes of the young

Similar variants

ABCC8 c.2116+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.3868-1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.3989-9G>A Pathogenic ★★ same condition
ABCC8 c.4308-2A>G Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Arg1379His Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Arg1538Gln Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Gly228Asp Pathogenic/Likely pathogenic ★★ same condition
ABCC8 p.Gly716Ser 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-ala315 (accessed [today's date]).

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