Is ABCC8 p.Ile1402Val (c.4204A>G) pathogenic?

ABCC8 p.Ile1402Val (c.4204A>G) is classified Uncertain significance in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.1928); Very rare (popmax 0.00585%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Ile1402Val (c.4204A>G)?

ABCC8 p.Ile1402Val (c.4204A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC8 p.Ile1402Val (c.4204A>G) in the general population?

ABCC8 p.Ile1402Val (c.4204A>G) is very rare (popmax 0.00585%, amr) (gnomAD).

What do computational predictors say about ABCC8 p.Ile1402Val (c.4204A>G)?

AlphaMissense predicts likely benign (score 0.1928) — an in-silico prediction, not a clinical call.

ABCC8 p.Ile1402Val

c.4204A>G · rs1413089349 · VCV3128904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00585%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1928	likely benign
REVEL	0.761	pathogenic-leaning
SaProt	LLR -9.04	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	23.9	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 0.00585% Admixed American · 3/51,242 alleles

Filtering AF 0.00155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000831%

Overall 0.000642% 9/1,401,930 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00585%	17,081
European (non-Finnish)	0.000522%	191,390

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.Ile1402Val
Coding: c.4204A>G
MANE Select: NM_000352
dbSNP: rs1413089349
Type: single nucleotide variant
Location: chr11:17395713 (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 1402: a β-strand; 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.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
ABCC8 p.Asp760Glu 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-ile1402val (accessed [today's date]).

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