Is ABCC8 p.Thr759= (c.2277C>T) pathogenic?

ABCC8 p.Thr759= (c.2277C>T) is classified Benign/Likely benign in ABCC8 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 5.19%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Thr759= (c.2277C>T)?

ABCC8 p.Thr759= (c.2277C>T) is associated with Inborn genetic diseases, hyperinsulinemic hypoglycemia, familial, 1, diabetes mellitus, transient neonatal, 2 (ClinVar).

ABCC8 p.Thr759=

Q: How common is ABCC8 p.Thr759= (c.2277C>T) in the general population?

ABCC8 p.Thr759= (c.2277C>T) is common (popmax 5.19%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2277C>T · rs1801261 · VCV157689

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 5.19%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

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 -6.1	GERP -3.6
Overall
CADD	0.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.19% European (non-Finnish) · 61,182/1,178,772 alleles

Filtering AF 5.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.14%

Overall 4.22% 67,971/1,610,186 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	5.19%	19
Amishnot grpmax-eligible	4.29%	23
Remaining individualsnot grpmax-eligible	3.37%	30
Finnishnot grpmax-eligible	3.11%	32
Admixed American	1.5%	67
Ashkenazi Jewishnot grpmax-eligible	0.978%	102
South Asian	0.946%	106
African / African-American	0.798%	125
Middle Eastern	0.413%	242
East Asian	0.0134%	7,466

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.Thr759=
Coding: c.2277C>T
MANE Select: NM_000352
dbSNP: rs1801261
Type: single nucleotide variant
Location: chr11:17415318 (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 759: the abc transporter 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hyperinsulinemic hypoglycemia, familial, 1 diabetes mellitus, transient neonatal, 2 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-thr759 (accessed [today's date]).

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