Is ABCC8 p.Glu501Ala (c.1502A>C) pathogenic?

ABCC8 p.Glu501Ala (c.1502A>C) is classified Likely pathogenic in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-29). AlphaMissense: likely pathogenic (0.9192); Very rare (popmax 8.47e-05%, nfe).

How common is ABCC8 p.Glu501Ala (c.1502A>C) in the general population?

ABCC8 p.Glu501Ala (c.1502A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABCC8 p.Glu501Ala (c.1502A>C)?

AlphaMissense predicts likely pathogenic (score 0.9192) — an in-silico prediction, not a clinical call.

ABCC8 p.Glu501Ala

c.1502A>C · rs749810368 · VCV2997719

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9192 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9192	likely pathogenic ✓ concordant with ClinVar
REVEL	0.973	strongly pathogenic-leaning
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 6.84e-05% 1/1,461,730 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.Glu501Ala
Coding: c.1502A>C
MANE Select: NM_000352
dbSNP: rs749810368
Type: single nucleotide variant
Location: chr11:17442848 (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 501: an α-helix; the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in hhf1)

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

Similar variants

ABCC8 p.Glu501Lys Pathogenic/Likely pathogenic ★★ same residue
ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.148+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.148+2T>G Likely pathogenic ★★ same type
ABCC8 c.1630+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.1630+1G>T Pathogenic ★★ same type
ABCC8 c.1817+1G>C Pathogenic ★★ same type

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-glu501ala (accessed [today's date]).

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