Is ABCC8 p.Ser611= (c.1833C>T) pathogenic?

ABCC8 p.Ser611= (c.1833C>T) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-11-12). Very rare (popmax 0.0011%, sas); Associated with maturity-onset diabetes of the young.

What condition is associated with ABCC8 p.Ser611= (c.1833C>T)?

ABCC8 p.Ser611= (c.1833C>T) is associated with maturity-onset diabetes of the young, transient neonatal diabetes mellitus (ClinVar).

How common is ABCC8 p.Ser611= (c.1833C>T) in the general population?

ABCC8 p.Ser611= (c.1833C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is MODY inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

ABCC8 p.Ser611=

c.1833C>T · rs763273046 · VCV1697228

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

maturity-onset diabetes of the young

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -5.5	GERP -4.1
Overall
CADD	1.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,090 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000868% 14/1,613,416 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
South Asiangrpmax	0.0011%	91,090
European (non-Finnish)	0.00102%	98,336

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser611=
Coding: c.1833C>T
MANE Select: NM_000352
dbSNP: rs763273046
Type: single nucleotide variant
Location: chr11:17428655 (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 611: an α-helix

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

Disease context

maturity-onset diabetes of the young — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: transient neonatal diabetes mellitus

For MODY (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ABCC8 p.Ser611Arg Uncertain significance ⚠ same residue
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

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-ser611 (accessed [today's date]).

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