Is ABCC8 p.Leu1450= (c.4350G>A) pathogenic?

ABCC8 p.Leu1450= (c.4350G>A) is classified Likely benign in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-16). Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Leu1450= (c.4350G>A)?

ABCC8 p.Leu1450= (c.4350G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC8 p.Leu1450= (c.4350G>A) in the general population?

ABCC8 p.Leu1450= (c.4350G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

ABCC8 p.Leu1450=

c.4350G>A · rs763277685 · VCV1614376

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 0.14	GERP -3.8, phastCons 0.94
Overall
CADD	7.948	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,770 alleles

Overall 0.000188% 3/1,599,496 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,770
South Asian	0.00113%	88,374
European (non-Finnish)	8.53e-05%	1,172,054

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.Leu1450=
Coding: c.4350G>A
MANE Select: NM_000352
dbSNP: rs763277685
Type: single nucleotide variant
Location: chr11:17395233 (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 1450: a UniProt-annotated variant site (in hhf1); an α-helix; the abc transporter 2 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

Similar variants

ABCC8 p.Leu1450Pro Conflicting classifications of pathogenicity ★ ⚠ 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-leu1450 (accessed [today's date]).

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