Is ABCC8 p.Ser1005= (c.3015C>T) pathogenic?

ABCC8 p.Ser1005= (c.3015C>T) is classified Likely benign in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-11). Very rare (popmax 0.00169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Ser1005= (c.3015C>T)?

ABCC8 p.Ser1005= (c.3015C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC8 p.Ser1005= (c.3015C>T) in the general population?

ABCC8 p.Ser1005= (c.3015C>T) is very rare (popmax 0.00169%, nfe) (gnomAD).

ABCC8 p.Ser1005=

c.3015C>T · rs2496531464 · VCV1798843

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -5.5
Overall
CADD	0.916	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,180,042 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00137% 20/1,461,838 alleles · very rare

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.Ser1005=
Coding: c.3015C>T
MANE Select: NM_000352
dbSNP: rs2496531464
Type: single nucleotide variant
Location: chr11:17407035 (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 1005: an α-helix

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

Similar variants

ABCC8 p.Ser1005Phe Uncertain significance ★ ⚠ same residue
ABCC8 p.Ser1005Thr Uncertain significance ⚠ same residue
ABCC8 p.Arg1250Ter Pathogenic ★★ same condition
ABCC8 c.1923+3G>A Uncertain significance ★★ same condition
ABCC8 p.Ala365Val Uncertain significance ★★ ⚠ same condition
ABCC8 p.Ala478Ser Uncertain significance ★★ ⚠ same condition
ABCC8 p.Arg657Gln Uncertain significance ★★ ⚠ same condition
ABCC8 p.Arg992Pro Uncertain significance ★★ ⚠ 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-ser1005 (accessed [today's date]).

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