Is ABCC8 p.Ala1007= (c.3021C>T) pathogenic?

ABCC8 p.Ala1007= (c.3021C>T) is classified Likely benign in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-17). Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Ala1007= (c.3021C>T)?

ABCC8 p.Ala1007= (c.3021C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC8 p.Ala1007= (c.3021C>T) in the general population?

ABCC8 p.Ala1007= (c.3021C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

ABCC8 p.Ala1007=

c.3021C>T · rs556199509 · VCV1661835

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.042	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.77 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.2	GERP -5.5
Overall
CADD	0.239	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000929% 15/1,614,168 alleles · very rare exomes 13/1,461,832 · genomes 2/152,336 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000932%	107,276

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.Ala1007=
Coding: c.3021C>T
MANE Select: NM_000352
dbSNP: rs556199509
Type: single nucleotide variant
Location: chr11:17407029 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 8 PDB

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.Ala1007Pro 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
ABCC8 p.Asp325Asn 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-ala1007 (accessed [today's date]).

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