Is ABCC8 p.Ala1390Pro (c.4168G>C) pathogenic?

ABCC8 p.Ala1390Pro (c.4168G>C) is classified Likely pathogenic in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-20). AlphaMissense: likely pathogenic (0.9926); Absent from gnomAD v4.1; Associated with hyperinsulinemic hypoglycemia, familial, 1.

What condition is associated with ABCC8 p.Ala1390Pro (c.4168G>C)?

ABCC8 p.Ala1390Pro (c.4168G>C) is associated with hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 p.Ala1390Pro (c.4168G>C) in the general population?

ABCC8 p.Ala1390Pro (c.4168G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC8 p.Ala1390Pro (c.4168G>C)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

ABCC8 p.Ala1390Pro

c.4168G>C · rs2496452651 · VCV1723123

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,591,820)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyperinsulinemic hypoglycemia, familial, 1

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic ✓ concordant with ClinVar · top 6% in ABCC8
REVEL	0.963	strongly pathogenic-leaning
SaProt	LLR -12.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,591,820). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCC8
Protein: p.Ala1390Pro
Coding: c.4168G>C
MANE Select: NM_000352
dbSNP: rs2496452651
Type: single nucleotide variant
Location: chr11:17395882 (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 1390: a turn; the abc transporter 2 domain

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

Disease context

hyperinsulinemic hypoglycemia, familial, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCC8 p.Ala1390= Likely benign ★ same residue
ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.148+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.148+2T>G Likely pathogenic ★★ same condition
ABCC8 c.1630+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1630+1G>T Pathogenic ★★ same condition
ABCC8 c.1817+2T>C 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-ala1390pro (accessed [today's date]).

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